Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been s...Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.展开更多
Objective Acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion.Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis.In t...Objective Acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion.Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis.In this study,we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition.Methods Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls.A systematic analysis of clinical characteristics and prognostic factors was also conducted.Cell growth was assessed using the Cell Counting Kit-8(CCK-8)assay,and apoptosis and cell cycle progression were evaluated by flow cytometry.Moreover,RNA pull-down was performed to identify target microRNAs,and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets.Results Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival(OS)(hazard ratio:2.357;95%confidence interval 1.258–4.415).The circ_0012152 knockdown reduced cell growth,increased apoptosis,and inhibited cell cycle progression in AML cell lines.RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152.Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors.We suggested that miR-652-3p targeted SOX4,as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells.Conclusion Circ_0012152 is an independent poor prognostic factor for OS in AML,and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.展开更多
Objective The metabolic reprogramming of acute myeloid leukemia(AML)cells is a compensatory adaptation to meet energy requirements for rapid proliferation.This study aimed to examine the synergistic effects of glutami...Objective The metabolic reprogramming of acute myeloid leukemia(AML)cells is a compensatory adaptation to meet energy requirements for rapid proliferation.This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells.Methods SKM-1 cells(an AML cell line)were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide(BPTES,a glutaminase inhibitor)or cytarabine.Cell viability was detected by Cell Counting Kit-8(CCK-8)assay,and cell apoptosis and reactive oxygen species(ROS)by flow cytometry.Western blotting was conducted to examine the levels of apoptotic proteins,including cleaved caspase-3 and poly(ADP-ribose)polymerase(PARP).Moreover,the human long noncoding RNA(lncRNA)microarray was used to analyze gene expression after glutamine deprivation,and results were confirmed with quantitative RT-PCR(qRT-PCR).The expression of metallothionein 2A(MT2A)was suppressed using siRNA.Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry,respectively,in cells with MT2A knockdown.Results Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells.The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation.MT2A knockdown increased apoptosis,while proliferation was not affected in SKM-1 cells.In addition,metformin inhibited cell growth and induced apoptosis in SKM-1 cells.Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine.Furthermore,the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells.Conclusion Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.展开更多
Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematop...Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.展开更多
BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have ...BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have always been unsatisfactory.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and transforming growth factor-β1(TGFβ1)expression and prognosis in older adults with AML.METHODS This study enrolled 80 patients with AML(AML group),including 36 with complete response(AML-CR),23 with partial response(AML-PR),and 21 with no response(AML-NR).The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls.Kaplan-Meier analysis was performed to assess overall survival(OS)and progression-or disease-free survival(DFS).Prognostic risk factors were analyzed using a Cox proportional hazards model.RESULTS The AML group showed a VEGF level of 2.68±0.16.VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR(P<0.05).TGFβ1 expression in the AML group was 0.33±0.05.Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR(P<0.05).VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes,platelets,hemoglobin,and peripheral blood immature cells(P<0.05);Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression(P<0.05),whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels(P<0.05).VEGF,TGFβ1,and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS(P<0.05),while VEGF,TGFβ1,and white blood cell count were independent risk factors for DFS(P<0.05).CONCLUSION Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.展开更多
Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with vene...Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.展开更多
Objective: To investigate the clinical efficacy of venetoclax in the treatment of elderly acute myeloid leukemia (AML). Methods: 50 cases of elderly AML patients receiving venetoclax for treatment in the hospital from...Objective: To investigate the clinical efficacy of venetoclax in the treatment of elderly acute myeloid leukemia (AML). Methods: 50 cases of elderly AML patients receiving venetoclax for treatment in the hospital from January 2022 to January 2024 were selected, including 38 cases of patients whose primary treatment was not suitable for intensive chemotherapy and 12 cases of relapsed/refractory AML patients, to observe the therapeutic efficacy and safety of venetoclax. Results: Among the 38 patients whose primary treatment was not suitable for intensive chemotherapy, 5 cases were treated with venetoclax monotherapy, 33 cases were treated with venetoclax + azacitidine, and 25 patients (65.79%) achieved complete remission (CR) with incomplete hematologic recovery (CRi) after 28 days of treatment;10 patients with relapsed/refractory AML were treated with venetoclax + azacitidine, and 2 patients were treated with venetoclax + azacitidine + chemotherapy, and 2 patients achieved optimal therapeutic response after 28 days of treatment and CR/CRi was achieved in 7 patients (58.33%). There were 47 (94.0%) patients with grade 3 or higher granulocytopenia, 46 (92.0%) patients with hemoglobin reduction, and 43 (86.0%) patients with thrombocytopenia, developed after 28 days of treatment. 11 patients developed infections after treatment and there was one case of tumor lysis syndrome. Conclusion: The response rate of venetoclax monotherapy and combination in elderly AML induction therapy is high, and the overall tolerability of elderly patients is good, so it can be popularized and applied.展开更多
Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity t...Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow (BM) niche is critical to the maintenance and retention of hematopoietic stem cells (HSC), including leukemia stem cells (LSC), and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy- induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDFI/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.展开更多
Summary: Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia (AML). The aim of this study was to examine the effect of res...Summary: Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia (AML). The aim of this study was to examine the effect of resveratrol-downregulated phosphorylated liver kinase B1 (pLKB1) on the senescence of acute myeloid leukemia (AML) stem cells. The protein expressions of pLKB 1 and Sirtuin 1 (SIRT1), a regulator ofpLKB1, were measured in CD34+CD38-KGla cells treated with resveratrol (40 μmol/L) or not by Western blotting. Senescence-related factors were examined, including p21 mRNA tested by real-time PCR, cell morphology by senescence-associated β-galactosidase (SA-β-gal) staining, cell pro- liferation by MTT assay and cell cycle by flow cytometry. Besides, apoptosis was flow cytometrically determined. The results showed that pLKB1 was highly expressed in CD34+CD38- KGla cells, and resveratrol, which could downregulate pLKB1 through activation of SIRT1, induced senescence and apoptosis of CD34+CD38- KGla cells. It was concluded that resveratrol-downregulated pLKB1 is in- volved in the senescence of AML stem cells.展开更多
The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use ...The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use of the key features shared with normal hematopoietic stem cells(HSCs) such as the capacity of self-renewal and the ability to initiate and sustain growth of progenitors in vivo. Significant progress has also been made in identifying the phenotype and signaling pathways specific for LSCs. Therapeutically, a multitude of drugs targeting LSCs are in different phases of preclinical and clinical development. This review focuses on recent discoveries which have advanced our understanding of LSC biology and provided rational targets for development of novel therapeutic agents. One of the major challenges is how to target the selfrenewal pathways of LSCs without affecting normal HSCs significantly therefore providing an acceptable therapeutic window. Important issues pertinent to the successful design and conduct of clinical trials evaluating drugs targeting LSCs will be discussed as well.展开更多
Objective: Intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML cases, is highly heterogeneous. We systematically summarize the latest research progress on the significa...Objective: Intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML cases, is highly heterogeneous. We systematically summarize the latest research progress on the significance ofgene mutations for prognostic stratification of IR-AML. Data Sources: We conducted a systemic search from the PubMed database up to October, 2014 using various search terms and their combinations including IR-AML, gene mutations, mutational analysis, prognosis, risk stratification, next generation sequencing (NGS). Study Selection: Clinical or basic research articles on NGS and the prognosis of gene mutations in 1R-AML were included. Results: The advent of the era of whole-genome sequencing has led to the discovery of an increasing number of molecular genetics aberrations that involved in leukemogenesis, and some of them have been used for prognostic risk stratification. Several studies have consistently identified that some gene mutations have prognostic relevance, however, there are still many controversies for some genes because of lacking sufficient evidence. In addition, tumor cells harbor hundreds of mutated genes and multiple mutations often coexist, therefore, single mutational analysis is not sufficient to make accurate prognostic predictions. The comprehensive analysis of multiple mutations based on sophisticated genomic technologies has raised increasing interest in recent years. Conclusions: NGS represents a pioneering and helpful approach to prognostic risk stratification of 1R-AML patients. Further large-scale studies for comprehensive molecular analysis are needed to provide guidance and a theoretical basis for IR-AML prognostic stratification and clinical management.展开更多
This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1(Dectin-1),Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),and myeloid differentiation primary response 88(MyDHH)i...This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1(Dectin-1),Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),and myeloid differentiation primary response 88(MyDHH)influence the susceptibility to pulmonary invasive fungal disease(IFD)in patients with acute myeloid leukemia(AML)from a Chinese Han population.Eight single nucleotide polymorphisms(SNPs)of Dectin-1(rs 16910526,rs3901533,and rs7309123),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)and MyD88(rs4988453 and rs4988457)in the genomic DNA of 172 adult AML patients were genotyped.Pulmonary IFD was diagnosed as proven or probable according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group(EORTC/MSG)consensus guidelines.SNPs that were significant in the univariate analysis were further analyzed using the multiple logistic regression analysis to determine their association with the occurrence of pulmonary IFD.The mRNA expression of Dectin-1 was detected according to the genotype by quantitative realtime PCR(qRT-PCR),and the correlation of this expression with the occurrence of pulmonary IFD in AML patients was analyzed.Two Dectin-1 intron SNPs(rs3901533 and rs7309123)were found to be significantly associated with the susceptibility to pulmonary IFD in AML patients in a Chinese Han population.Significant associations were noted between pulmonary IFD and Dectin-1 rs3901533 dominant model(G/T+G/G vs.T/T,OR:2.158;95%Cl:1.109-4.2,P=0.02),Dectin-1 rs3901533 G allele(OR:2.201;95%Cl:1.206-4.019,P=0.01),or Dectin-1 rs7309123 C allele(OR:1.919;95%Cl:1.047-3.518,P=0.03).There were no significant associations between pulmonary IFD and the remaining Dectin-1 SNPs(rs 16910526),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)or MyDHH(rs4988453 and rs4988457).In conclusion,two Dectin-1 SNPs(rs3901533 and rs7309123)are associated with increased susceptibility to pulmonary IFD in AML patients in a Chinese Han population.展开更多
BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for...BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.展开更多
BACKGROUND Acute myeloid leukemia(AML)is one of the most common types of leukemia in adults.However,AML is relatively rare in the population overall,accounting for only about 1 percent of all cancers.Treatment for AML...BACKGROUND Acute myeloid leukemia(AML)is one of the most common types of leukemia in adults.However,AML is relatively rare in the population overall,accounting for only about 1 percent of all cancers.Treatment for AML can be very effective for some patients,yet it leaves others with serious and even life-threatening side effects.Chemotherapy is still the primary treatment for most AML,but over time,leukemia cells become resistant to chemotherapy drugs.In addition,stem cell transplantation,targeted therapy,and immunotherapy are currently available.At the same time,with the progression of the disease,the patient may have corresponding complications,such as coagulation dysfunction,anemia,granulocytopenia,and repeated infection,so transfusion supportive therapy will be involved in the overall treatment regime.To date,few articles have reported on blood transfusion treatment options for patients with ABO subtypes AML-M2.Blood transfusion therapy is an important supportive treatment for AML-M2,and accurate determination of patients'blood type is one of the most important steps in the treatment process.In this study,we explored blood typing and supportive treatment strategies for a patient with A2 subtype AML-M2 to provide the basis for treatment for all patients.CASE SUMMARY In order to determine the blood type of the patient,serological and molecular biological methods were used for reference tests,and the genetic background was studied to determine the patient's final blood type and select the appropriate blood products for infusion treatment.According to the results obtained by serological and molecular biological methods,the blood type of the patient was A2 subtype;the genotype was A02/001;the irregular antibody screening was negative,and anti-A1 was found in the plasma.According to the overall treatment plan,active anti-infection,elevated cells,component blood transfusion support,and other rescue and supportive treatments were given,and the patient successfully passed the stage of myelosuppression after chemotherapy.Re-examination of bone marrow smears showed that AL was in complete remission of bone marrow signs,and minimal residual leukemia lesions suggested no cells with obvious abnormal immunophenotype(residual leukemia cells<10-4).CONCLUSION The infusion of patients with A2 subtype AML-M2 with A irradiated platelets and O washing red blood cells can meet the needs of clinical treatment.展开更多
Primary pulmonary leiomyosarcoma (LMS) is a very unusual tumor.Although LMS has well-known metastatic potential,cutaneous metastasis is a remarkably uncommon.Exposure to cytotoxic agents could lead to "therapy-rela...Primary pulmonary leiomyosarcoma (LMS) is a very unusual tumor.Although LMS has well-known metastatic potential,cutaneous metastasis is a remarkably uncommon.Exposure to cytotoxic agents could lead to "therapy-related myeloid neoplasm" (t-MN).Starting from 2008,the World Health Organization (WHO) has adopted the term to cover the spectrum of malignant diseases previously known as therapy-related acute myeloid leukemia (t-AML),therapy-related myelodysplastic syndrome (t-MDS) and therapy-related myelodysplastic/myelo-proliferative neoplasm (t-MDS/MPN).We described the onset of t-MDS and progression to t-AML in one case diagnosed as primary pulmonary LMS with cutaneous metastasis.This patient achieved complete remission (CR) after three courses of IA regimen chemotherapy (idarubicin 5 mg/d,d 1-3;cytarabine 100 mg/d,d 1-5) and 1 course of HA chemotherapy regimen (homoharringtonine 3 mg/d,d 1-3;cytarabine 100 mg/d,d 1-7).This case presents the natural course of therapy-related neoplasm and provides therapeutic experience for t-AML.展开更多
Objective: To investigate the association between the T cell inhibitory receptor programmed death 1(PD-1)and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia(AML) and AML in c...Objective: To investigate the association between the T cell inhibitory receptor programmed death 1(PD-1)and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia(AML) and AML in complete remission(CR).Methods:Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3+,CD4+ and CD8+ T cells from peripheral blood samples from 20 newly diagnosed,untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry.Twenty-three healthy individuals served as control.Results:A significantly higher percentage of PD-1+ cells were found for CD3+ T cells in the de novo AML group compared with healthy controls.In addition,an increased level of PD-1+ CD8+ T cells,but not PD-1+ CD4+,was found for CD3+ T cells in the de novo AML and AML-CR samples.A higher percentage of CD244+ CD4+,CD244+ CD8+,CD57+ CD4+ and CD57+ CD8+ T cells was found in CD3+ T cells in samples from those with de novo AML compared with those from healthy controls.Strong increased PD-1+ CD244+ and PD-1+ CD57+ coexpression was found for CD4+ and CD8+ T cells in the de novo AML group compared with healthy controls.Conclusions:We characterized the major T cell defects,including co-expression of PD-1 and CD244,CD57-exhausted T cells in patients with de novo AML,and found a particular influence on CD8+ T cells,suggesting a poor anti-leukemia immune response in these patients.展开更多
Nowadays the role of genetic findings in determining the diagnosis,therapy and prognosis of acute myeloid leukemia(AML) has become more valuable.To improve and validate the detection of clonal chromosomal aberrations ...Nowadays the role of genetic findings in determining the diagnosis,therapy and prognosis of acute myeloid leukemia(AML) has become more valuable.To improve and validate the detection of clonal chromosomal aberrations in leukemia,we designed a combined application of karyotyping with multiplex reverse transcription-polymerase chain reaction(RT-PCR) and fluorescence in situ hybridization(FISH),and addressed the expression and distribution of fusion genes among the subtypes of Chinese adult patients with de novo AML.Multiplex RT-PCR assays were performed on 477 samples from newly diagnosed AML patients,and cytogenetic data were obtained from 373 of them by R or G banding techniques and those in some cases were confirmed by FISH.The PCR products in some suspected cases were tested by two-directional sequencing.The results showed that except unqualified samples,fusion genes were detected by multiplex RT-PCR in 211 of 474 patients(44.51%),including AML1-ETO,CBFβ-MYH11,PML-RARα,PLZF-RARα,NPM-RARα,MLL rearrangements,BCR-ABL,DEK-CAN,SET-CAN,TEL-PDGFR,TLS-ERG,AML1-MDS1(EVI-1).In 373 patients,who took both multiplex RT-PCR and karyotype analysis,the detection rate of chromosomal aberrations by using multiplex RT-PCR and karyotyping was 160/373(42.89%) and 179/373(47.98%) respectively,and the combination could optimize the detection rate of clonal genetic abnormalities to 216/373(57.90%).The PCR results from 11 cases 'normal' in karyotyping but abnormal in RT-PCR for MLL rearrangements were confirmed by two-directional sequencing.It is concluded that karyotype studies remain the cornerstone for genetic testing;conventional cytogenetics and molecular-based methods are complementary tests for the detection of clonal genetic aberrations in AML,especially for the cryptic or submicroscopic aberrations.Once a genetic marker has been identified by combined analysis,it could be used to monitor residual disease during/after chemotherapy,by quantitative RT-PCR and/or FISH.展开更多
Acute myeloid leukemia(AML) is a clonal disorder characterized by the accumulation of complex genomic alterations that define the disease pathophysiology and overall outcome. Recent advances in sequencing technologies...Acute myeloid leukemia(AML) is a clonal disorder characterized by the accumulation of complex genomic alterations that define the disease pathophysiology and overall outcome. Recent advances in sequencing technologies have described the molecular landscape of AML and identified several somatic alterations that impact overall survival. Despite all these advancement, several challenges remain in translating this information into effective therapy. Herein we will review the molecular landscape of AML and discuss the impact of the most common somatic mutations on disease biology and outcome.展开更多
In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine(HAM) with that of high-dose cytarabine alone(Hi DAC) as consolidation regimens in non-acute promyelocytic leu...In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine(HAM) with that of high-dose cytarabine alone(Hi DAC) as consolidation regimens in non-acute promyelocytic leukemia(APL) acute myeloid leukemia patients with favorable and intermediate cytogenetics.A total of 62 patients from Shenzhen People's Hospital were enrolled in this study.All patients enrolled received standard induction chemotherapy and achieved the first complete remission(CR1).In these patients,24 received Hi DAC and 38 received HAM as consolidation.The median relapse free survival(RFS) and overall survival(OS) were similar between these two consolidation regimens.Even in subgroup analysis according to risk stratification,the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics.However,in patients receiving HAM regimen,the lowest neutrophil count was lower,neutropenic period longer,neutropenic fever rate higher,and more platelet transfusion support was required.HAM group also tended to have higher rate of sepsis than Hi DAC group.According to our results,we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to Hi DAC,even in young non-APL AML patients with favorable and intermediate cytogenetics.展开更多
BACKGROUND The concurrence of acute myeloid leukemia(AML)and chronic lymphocytic leukemia(CLL)is rare.Previous reports of such cases have focused mainly on clinical diagnosis and characteristics,so the mechanism remai...BACKGROUND The concurrence of acute myeloid leukemia(AML)and chronic lymphocytic leukemia(CLL)is rare.Previous reports of such cases have focused mainly on clinical diagnosis and characteristics,so the mechanism remains unclear,and therapy options have been poorly explored.CASE SUMMARY Here,we report two cases of synchronous AML and CLL.Flow cytometry revealed two distinct abnormal cell populations(myeloblasts and lymphoid cells)according to scatter characteristics.CD5-positive B cell lymphoma with myeloid leukemia invasion was observed on lymph node biopsy.Chemotherapy regimens indicated for both AML and CLL were used in our patients,and our patients achieved complete response after chemotherapy.Next-generation sequencing of 88 genes was performed.CONCLUSION We conclude that early mutation and dysregulation at the hematopoietic stem cell stage and the accumulation of multiple rearrangements may cause the concurrence of CLL and AML.The treatment of infection and combination therapy aimed at the CLL component are significant in the management of patients with concurrent CLL and AML.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.32200590 to K.L.,81972358 to Q.W.,91959113 to Q.W.,and 82372897 to Q.W.)the Natural Science Foundation of Jiangsu Province(Grant No.BK20210530 to K.L.).
文摘Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.
基金supported by grants from the Natural Science Foundation of Zhejiang Province(No.LY20H080001)Medical and Health Science and Technology Projects of Zhejiang Province(No.2021KY997,No.2022KY306,No.2022KY316,No.2023KY263).
文摘Objective Acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion.Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis.In this study,we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition.Methods Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls.A systematic analysis of clinical characteristics and prognostic factors was also conducted.Cell growth was assessed using the Cell Counting Kit-8(CCK-8)assay,and apoptosis and cell cycle progression were evaluated by flow cytometry.Moreover,RNA pull-down was performed to identify target microRNAs,and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets.Results Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival(OS)(hazard ratio:2.357;95%confidence interval 1.258–4.415).The circ_0012152 knockdown reduced cell growth,increased apoptosis,and inhibited cell cycle progression in AML cell lines.RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152.Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors.We suggested that miR-652-3p targeted SOX4,as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells.Conclusion Circ_0012152 is an independent poor prognostic factor for OS in AML,and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.
基金supported by the National Natural Science Foundation of China(No.82270177).
文摘Objective The metabolic reprogramming of acute myeloid leukemia(AML)cells is a compensatory adaptation to meet energy requirements for rapid proliferation.This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells.Methods SKM-1 cells(an AML cell line)were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide(BPTES,a glutaminase inhibitor)or cytarabine.Cell viability was detected by Cell Counting Kit-8(CCK-8)assay,and cell apoptosis and reactive oxygen species(ROS)by flow cytometry.Western blotting was conducted to examine the levels of apoptotic proteins,including cleaved caspase-3 and poly(ADP-ribose)polymerase(PARP).Moreover,the human long noncoding RNA(lncRNA)microarray was used to analyze gene expression after glutamine deprivation,and results were confirmed with quantitative RT-PCR(qRT-PCR).The expression of metallothionein 2A(MT2A)was suppressed using siRNA.Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry,respectively,in cells with MT2A knockdown.Results Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells.The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation.MT2A knockdown increased apoptosis,while proliferation was not affected in SKM-1 cells.In addition,metformin inhibited cell growth and induced apoptosis in SKM-1 cells.Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine.Furthermore,the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells.Conclusion Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.
基金supported by the Key Program of the National Natural Science Foundation of China(No.81930004)the National Natural Science Foundation of China(No.82170208)+2 种基金Tongzhou District Distinguished Young Scholars(No.JCQN2023009)Plan Project of Tongzhou Municipal Science and Technology(No.KJ2024CX045)Beijing Natural Science Foundation(No.Z230016)。
文摘Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.
基金the Ethic Committee of Suzhou Hospital of Anhui Medical University(Approval No.C2024003).
文摘BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have always been unsatisfactory.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and transforming growth factor-β1(TGFβ1)expression and prognosis in older adults with AML.METHODS This study enrolled 80 patients with AML(AML group),including 36 with complete response(AML-CR),23 with partial response(AML-PR),and 21 with no response(AML-NR).The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls.Kaplan-Meier analysis was performed to assess overall survival(OS)and progression-or disease-free survival(DFS).Prognostic risk factors were analyzed using a Cox proportional hazards model.RESULTS The AML group showed a VEGF level of 2.68±0.16.VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR(P<0.05).TGFβ1 expression in the AML group was 0.33±0.05.Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR(P<0.05).VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes,platelets,hemoglobin,and peripheral blood immature cells(P<0.05);Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression(P<0.05),whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels(P<0.05).VEGF,TGFβ1,and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS(P<0.05),while VEGF,TGFβ1,and white blood cell count were independent risk factors for DFS(P<0.05).CONCLUSION Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.
文摘Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.
文摘Objective: To investigate the clinical efficacy of venetoclax in the treatment of elderly acute myeloid leukemia (AML). Methods: 50 cases of elderly AML patients receiving venetoclax for treatment in the hospital from January 2022 to January 2024 were selected, including 38 cases of patients whose primary treatment was not suitable for intensive chemotherapy and 12 cases of relapsed/refractory AML patients, to observe the therapeutic efficacy and safety of venetoclax. Results: Among the 38 patients whose primary treatment was not suitable for intensive chemotherapy, 5 cases were treated with venetoclax monotherapy, 33 cases were treated with venetoclax + azacitidine, and 25 patients (65.79%) achieved complete remission (CR) with incomplete hematologic recovery (CRi) after 28 days of treatment;10 patients with relapsed/refractory AML were treated with venetoclax + azacitidine, and 2 patients were treated with venetoclax + azacitidine + chemotherapy, and 2 patients achieved optimal therapeutic response after 28 days of treatment and CR/CRi was achieved in 7 patients (58.33%). There were 47 (94.0%) patients with grade 3 or higher granulocytopenia, 46 (92.0%) patients with hemoglobin reduction, and 43 (86.0%) patients with thrombocytopenia, developed after 28 days of treatment. 11 patients developed infections after treatment and there was one case of tumor lysis syndrome. Conclusion: The response rate of venetoclax monotherapy and combination in elderly AML induction therapy is high, and the overall tolerability of elderly patients is good, so it can be popularized and applied.
基金funding from Guangzhou Pearl River of Science & Technology New Star (Grant No. 2011J2200069)supported in part by grants from the National Institutes of Health (Grant No. P01 CA055164)+2 种基金MD Anderson Cancer Center Support (Grant No. CA016672)the Paul and Mary Haas Chair in Genetics to Michael Andreeffby the University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center to Bing Z. Carter
文摘Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow (BM) niche is critical to the maintenance and retention of hematopoietic stem cells (HSC), including leukemia stem cells (LSC), and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy- induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDFI/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.
基金supported by grants from the National Natural Science Foundation of China(Nos.81370660,81170524)
文摘Summary: Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia (AML). The aim of this study was to examine the effect of resveratrol-downregulated phosphorylated liver kinase B1 (pLKB1) on the senescence of acute myeloid leukemia (AML) stem cells. The protein expressions of pLKB 1 and Sirtuin 1 (SIRT1), a regulator ofpLKB1, were measured in CD34+CD38-KGla cells treated with resveratrol (40 μmol/L) or not by Western blotting. Senescence-related factors were examined, including p21 mRNA tested by real-time PCR, cell morphology by senescence-associated β-galactosidase (SA-β-gal) staining, cell pro- liferation by MTT assay and cell cycle by flow cytometry. Besides, apoptosis was flow cytometrically determined. The results showed that pLKB1 was highly expressed in CD34+CD38- KGla cells, and resveratrol, which could downregulate pLKB1 through activation of SIRT1, induced senescence and apoptosis of CD34+CD38- KGla cells. It was concluded that resveratrol-downregulated pLKB1 is in- volved in the senescence of AML stem cells.
文摘The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use of the key features shared with normal hematopoietic stem cells(HSCs) such as the capacity of self-renewal and the ability to initiate and sustain growth of progenitors in vivo. Significant progress has also been made in identifying the phenotype and signaling pathways specific for LSCs. Therapeutically, a multitude of drugs targeting LSCs are in different phases of preclinical and clinical development. This review focuses on recent discoveries which have advanced our understanding of LSC biology and provided rational targets for development of novel therapeutic agents. One of the major challenges is how to target the selfrenewal pathways of LSCs without affecting normal HSCs significantly therefore providing an acceptable therapeutic window. Important issues pertinent to the successful design and conduct of clinical trials evaluating drugs targeting LSCs will be discussed as well.
基金a grant from the National Natural Science Foundation of China
文摘Objective: Intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML cases, is highly heterogeneous. We systematically summarize the latest research progress on the significance ofgene mutations for prognostic stratification of IR-AML. Data Sources: We conducted a systemic search from the PubMed database up to October, 2014 using various search terms and their combinations including IR-AML, gene mutations, mutational analysis, prognosis, risk stratification, next generation sequencing (NGS). Study Selection: Clinical or basic research articles on NGS and the prognosis of gene mutations in 1R-AML were included. Results: The advent of the era of whole-genome sequencing has led to the discovery of an increasing number of molecular genetics aberrations that involved in leukemogenesis, and some of them have been used for prognostic risk stratification. Several studies have consistently identified that some gene mutations have prognostic relevance, however, there are still many controversies for some genes because of lacking sufficient evidence. In addition, tumor cells harbor hundreds of mutated genes and multiple mutations often coexist, therefore, single mutational analysis is not sufficient to make accurate prognostic predictions. The comprehensive analysis of multiple mutations based on sophisticated genomic technologies has raised increasing interest in recent years. Conclusions: NGS represents a pioneering and helpful approach to prognostic risk stratification of 1R-AML patients. Further large-scale studies for comprehensive molecular analysis are needed to provide guidance and a theoretical basis for IR-AML prognostic stratification and clinical management.
基金the National Natural Science Foundation of China(No.81500105).
文摘This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1(Dectin-1),Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),and myeloid differentiation primary response 88(MyDHH)influence the susceptibility to pulmonary invasive fungal disease(IFD)in patients with acute myeloid leukemia(AML)from a Chinese Han population.Eight single nucleotide polymorphisms(SNPs)of Dectin-1(rs 16910526,rs3901533,and rs7309123),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)and MyD88(rs4988453 and rs4988457)in the genomic DNA of 172 adult AML patients were genotyped.Pulmonary IFD was diagnosed as proven or probable according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group(EORTC/MSG)consensus guidelines.SNPs that were significant in the univariate analysis were further analyzed using the multiple logistic regression analysis to determine their association with the occurrence of pulmonary IFD.The mRNA expression of Dectin-1 was detected according to the genotype by quantitative realtime PCR(qRT-PCR),and the correlation of this expression with the occurrence of pulmonary IFD in AML patients was analyzed.Two Dectin-1 intron SNPs(rs3901533 and rs7309123)were found to be significantly associated with the susceptibility to pulmonary IFD in AML patients in a Chinese Han population.Significant associations were noted between pulmonary IFD and Dectin-1 rs3901533 dominant model(G/T+G/G vs.T/T,OR:2.158;95%Cl:1.109-4.2,P=0.02),Dectin-1 rs3901533 G allele(OR:2.201;95%Cl:1.206-4.019,P=0.01),or Dectin-1 rs7309123 C allele(OR:1.919;95%Cl:1.047-3.518,P=0.03).There were no significant associations between pulmonary IFD and the remaining Dectin-1 SNPs(rs 16910526),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)or MyDHH(rs4988453 and rs4988457).In conclusion,two Dectin-1 SNPs(rs3901533 and rs7309123)are associated with increased susceptibility to pulmonary IFD in AML patients in a Chinese Han population.
文摘BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.
文摘BACKGROUND Acute myeloid leukemia(AML)is one of the most common types of leukemia in adults.However,AML is relatively rare in the population overall,accounting for only about 1 percent of all cancers.Treatment for AML can be very effective for some patients,yet it leaves others with serious and even life-threatening side effects.Chemotherapy is still the primary treatment for most AML,but over time,leukemia cells become resistant to chemotherapy drugs.In addition,stem cell transplantation,targeted therapy,and immunotherapy are currently available.At the same time,with the progression of the disease,the patient may have corresponding complications,such as coagulation dysfunction,anemia,granulocytopenia,and repeated infection,so transfusion supportive therapy will be involved in the overall treatment regime.To date,few articles have reported on blood transfusion treatment options for patients with ABO subtypes AML-M2.Blood transfusion therapy is an important supportive treatment for AML-M2,and accurate determination of patients'blood type is one of the most important steps in the treatment process.In this study,we explored blood typing and supportive treatment strategies for a patient with A2 subtype AML-M2 to provide the basis for treatment for all patients.CASE SUMMARY In order to determine the blood type of the patient,serological and molecular biological methods were used for reference tests,and the genetic background was studied to determine the patient's final blood type and select the appropriate blood products for infusion treatment.According to the results obtained by serological and molecular biological methods,the blood type of the patient was A2 subtype;the genotype was A02/001;the irregular antibody screening was negative,and anti-A1 was found in the plasma.According to the overall treatment plan,active anti-infection,elevated cells,component blood transfusion support,and other rescue and supportive treatments were given,and the patient successfully passed the stage of myelosuppression after chemotherapy.Re-examination of bone marrow smears showed that AL was in complete remission of bone marrow signs,and minimal residual leukemia lesions suggested no cells with obvious abnormal immunophenotype(residual leukemia cells<10-4).CONCLUSION The infusion of patients with A2 subtype AML-M2 with A irradiated platelets and O washing red blood cells can meet the needs of clinical treatment.
文摘Primary pulmonary leiomyosarcoma (LMS) is a very unusual tumor.Although LMS has well-known metastatic potential,cutaneous metastasis is a remarkably uncommon.Exposure to cytotoxic agents could lead to "therapy-related myeloid neoplasm" (t-MN).Starting from 2008,the World Health Organization (WHO) has adopted the term to cover the spectrum of malignant diseases previously known as therapy-related acute myeloid leukemia (t-AML),therapy-related myelodysplastic syndrome (t-MDS) and therapy-related myelodysplastic/myelo-proliferative neoplasm (t-MDS/MPN).We described the onset of t-MDS and progression to t-AML in one case diagnosed as primary pulmonary LMS with cutaneous metastasis.This patient achieved complete remission (CR) after three courses of IA regimen chemotherapy (idarubicin 5 mg/d,d 1-3;cytarabine 100 mg/d,d 1-5) and 1 course of HA chemotherapy regimen (homoharringtonine 3 mg/d,d 1-3;cytarabine 100 mg/d,d 1-7).This case presents the natural course of therapy-related neoplasm and provides therapeutic experience for t-AML.
基金supported by grants from the National Natural Science Foundation of China (No. 81570143 and 91642111)the Guangdong Provincial Basic Research Program (No. 2015B020227003)+3 种基金the Guangdong Provincial Applied Science and Technology Research & Development Program (No. 2016B020237006)the Guangzhou Science and Technology Project (No. 201510010211)the Fundamental Research Funds for the Central Universities (No. 21616108)the Medical Scientific Research Foundation of Guangdong Province, China (No. A2016045)
文摘Objective: To investigate the association between the T cell inhibitory receptor programmed death 1(PD-1)and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia(AML) and AML in complete remission(CR).Methods:Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3+,CD4+ and CD8+ T cells from peripheral blood samples from 20 newly diagnosed,untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry.Twenty-three healthy individuals served as control.Results:A significantly higher percentage of PD-1+ cells were found for CD3+ T cells in the de novo AML group compared with healthy controls.In addition,an increased level of PD-1+ CD8+ T cells,but not PD-1+ CD4+,was found for CD3+ T cells in the de novo AML and AML-CR samples.A higher percentage of CD244+ CD4+,CD244+ CD8+,CD57+ CD4+ and CD57+ CD8+ T cells was found in CD3+ T cells in samples from those with de novo AML compared with those from healthy controls.Strong increased PD-1+ CD244+ and PD-1+ CD57+ coexpression was found for CD4+ and CD8+ T cells in the de novo AML group compared with healthy controls.Conclusions:We characterized the major T cell defects,including co-expression of PD-1 and CD244,CD57-exhausted T cells in patients with de novo AML,and found a particular influence on CD8+ T cells,suggesting a poor anti-leukemia immune response in these patients.
文摘Nowadays the role of genetic findings in determining the diagnosis,therapy and prognosis of acute myeloid leukemia(AML) has become more valuable.To improve and validate the detection of clonal chromosomal aberrations in leukemia,we designed a combined application of karyotyping with multiplex reverse transcription-polymerase chain reaction(RT-PCR) and fluorescence in situ hybridization(FISH),and addressed the expression and distribution of fusion genes among the subtypes of Chinese adult patients with de novo AML.Multiplex RT-PCR assays were performed on 477 samples from newly diagnosed AML patients,and cytogenetic data were obtained from 373 of them by R or G banding techniques and those in some cases were confirmed by FISH.The PCR products in some suspected cases were tested by two-directional sequencing.The results showed that except unqualified samples,fusion genes were detected by multiplex RT-PCR in 211 of 474 patients(44.51%),including AML1-ETO,CBFβ-MYH11,PML-RARα,PLZF-RARα,NPM-RARα,MLL rearrangements,BCR-ABL,DEK-CAN,SET-CAN,TEL-PDGFR,TLS-ERG,AML1-MDS1(EVI-1).In 373 patients,who took both multiplex RT-PCR and karyotype analysis,the detection rate of chromosomal aberrations by using multiplex RT-PCR and karyotyping was 160/373(42.89%) and 179/373(47.98%) respectively,and the combination could optimize the detection rate of clonal genetic abnormalities to 216/373(57.90%).The PCR results from 11 cases 'normal' in karyotyping but abnormal in RT-PCR for MLL rearrangements were confirmed by two-directional sequencing.It is concluded that karyotype studies remain the cornerstone for genetic testing;conventional cytogenetics and molecular-based methods are complementary tests for the detection of clonal genetic aberrations in AML,especially for the cryptic or submicroscopic aberrations.Once a genetic marker has been identified by combined analysis,it could be used to monitor residual disease during/after chemotherapy,by quantitative RT-PCR and/or FISH.
文摘Acute myeloid leukemia(AML) is a clonal disorder characterized by the accumulation of complex genomic alterations that define the disease pathophysiology and overall outcome. Recent advances in sequencing technologies have described the molecular landscape of AML and identified several somatic alterations that impact overall survival. Despite all these advancement, several challenges remain in translating this information into effective therapy. Herein we will review the molecular landscape of AML and discuss the impact of the most common somatic mutations on disease biology and outcome.
基金supported by grants from the Basic Research Project of Shenzhen Science and Technology Program(No.JYCJ20150403101146307,No.JCYJ20150403101028195 and No.JCYJ20160422145031770)the National Natural Science Foundation of China(No.81600168)
文摘In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine(HAM) with that of high-dose cytarabine alone(Hi DAC) as consolidation regimens in non-acute promyelocytic leukemia(APL) acute myeloid leukemia patients with favorable and intermediate cytogenetics.A total of 62 patients from Shenzhen People's Hospital were enrolled in this study.All patients enrolled received standard induction chemotherapy and achieved the first complete remission(CR1).In these patients,24 received Hi DAC and 38 received HAM as consolidation.The median relapse free survival(RFS) and overall survival(OS) were similar between these two consolidation regimens.Even in subgroup analysis according to risk stratification,the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics.However,in patients receiving HAM regimen,the lowest neutrophil count was lower,neutropenic period longer,neutropenic fever rate higher,and more platelet transfusion support was required.HAM group also tended to have higher rate of sepsis than Hi DAC group.According to our results,we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to Hi DAC,even in young non-APL AML patients with favorable and intermediate cytogenetics.
文摘BACKGROUND The concurrence of acute myeloid leukemia(AML)and chronic lymphocytic leukemia(CLL)is rare.Previous reports of such cases have focused mainly on clinical diagnosis and characteristics,so the mechanism remains unclear,and therapy options have been poorly explored.CASE SUMMARY Here,we report two cases of synchronous AML and CLL.Flow cytometry revealed two distinct abnormal cell populations(myeloblasts and lymphoid cells)according to scatter characteristics.CD5-positive B cell lymphoma with myeloid leukemia invasion was observed on lymph node biopsy.Chemotherapy regimens indicated for both AML and CLL were used in our patients,and our patients achieved complete response after chemotherapy.Next-generation sequencing of 88 genes was performed.CONCLUSION We conclude that early mutation and dysregulation at the hematopoietic stem cell stage and the accumulation of multiple rearrangements may cause the concurrence of CLL and AML.The treatment of infection and combination therapy aimed at the CLL component are significant in the management of patients with concurrent CLL and AML.