Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report

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.

Adult rhabdomyosarcoma combined with acute myeloid leukemia: A case report

BACKGROUND Rhabdomyosarcoma is a tumor of mesenchymal origin.Secondary leukemia is a complication of previous transformation to other hematologic disorders or is a treatment-related acute myeloid leukemia secondary to cytotoxic chemotherapy or radiation therapy for other malignancies.CASE SUMMARY We present the case of a 36-year-old female patient who was diagnosed with rhabdomyosarcoma and acute myeloid leukemia.Further disease progression was observed after multiline chemotherapy.Eventually,the patient suffered cerebral hemorrhage,which resulted in death.CONCLUSION The incidence of rhabdomyosarcoma in adults is extremely low,and secondary leukemia caused by rhabdomyosarcoma is even rarer.Secondary leukemia has a very poor prognosis and a low overall survival rate.

Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia

Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients.Methods:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations.Conclusion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

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.

Damage Mechanism of CK2 and IKAROS in Philadelphia Like Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lymphoid progenitor cells, pro-B cells, pre-B cells, and mature cells). The process of B cell maturation depends on precise communication within the cell: signals activate specific genes that are essential for proper development. Errors in this intricate signaling network can lead to issues with B cell function and contribute to disease. B-lineage acute lymphoid leukemias, malignancies of precursor-stage B lymphoid cells inhibit lymphoid differentiation, leading to abnormal cell proliferation and survival. The process of developing leukemia (leukemogenesis) can be triggered by an overproduction of both hematopoietic stem cells (the cells that form all blood cells) and the immature versions of white blood cells called lymphoblasts. Acute lymphoblastic leukemia (ALL) with the presence of the Philadelphia chromosome (ALL Ph) is classified as a high-risk manifestation of the disease, this chromosome is the product of the reciprocal translocation, whose product is a BCR-ABL fusion protein. It is a highly active tyrosine kinase that can transform hematopoietic cells into cytokine-independent. Hyperphosphorylation cascades inhibit the differentiating function of IKZF1 as a tumor suppressor gene which leads to an abnormal proliferation of B cells due to the presence of the Philadelphia chromosome;it inhibits the differentiating process, leukemogenesis involving immature B cells in the bloodstream can result from the uncontrolled growth and division of hematopoietic stem cells and immature lymphoblasts (the precursors to B cells).

Incidence and Survivability of Acute Lymphocytic Leukemia Patients in the United States: Analysis of SEER Data Set from 2000-2019

The main goal of this research is to assess the impact of race, age at diagnosis, sex, and phenotype on the incidence and survivability of acute lymphocytic leukemia (ALL) among patients in the United States. By taking these factors into account, the study aims to explore how existing cancer registry data can aid in the early detection and effective treatment of ALL in patients. Our hypothesis was that statistically significant correlations exist between race, age at which patients were diagnosed, sex, and phenotype of the ALL patients, and their rate of incidence and survivability data were evaluated using SEER*Stat statistical software from National Cancer Institute. Analysis of the incidence data revealed that a higher prevalence of ALL was among the Caucasian population. The majority of ALL cases (59%) occurred in patients aged between 0 to 19 years at the time of diagnosis, and 56% of the affected individuals were male. The B-cell phenotype was predominantly associated with ALL cases (73%). When analyzing survivability data, it was observed that the 5-year survival rates slightly exceeded the 10-year survival rates for the respective demographics. Survivability rates of African Americans patients were the lowest compared to Caucasian, Asian, Pacific Islanders, Alaskan Native, Native Americans and others. Survivability rates progressively decreased for older patients. Moreover, this study investigated the typical treatment methods applied to ALL patients, mainly comprising chemotherapy, with occasional supplementation of radiation therapy as required. The study demonstrated the considerable efficacy of chemotherapy in enhancing patients’ chances of survival, while those who remained untreated faced a less favorable prognosis from the disease. Although a significant amount of data and information exists, this study can help doctors in the future by diagnosing patients with certain characteristics. It will further assist the health care professionals in screening potential patients and early detection of cases. This could also save the lives of elderly patients who have a higher mortality rate from this disease.

Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis

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.

Bone marrow microRNA-34a is a good indicator for response to treatment in acute myeloid leukemia

Background:microRNA 34a(miR 34a)had been reported to have a diagnostic role in acute myeloid leukemia(AML).However,its value in the bone marrow(BM)of AML patients,in addition to its role in response to therapy is still unclear.The current study was designed to assess the diagnostic,prognostic,and predictive significance of miR 34a in the BM of AML patients.Methods:The miR.34a was assed in BM aspirate of 82 AML patients in relation to 12 normal control subjects using qRT-PCR.The data were assessed for correlation with the relevant dinical critenia,response to therapy,disease-free survival(DFS),and overall survival(OS)rates.Results:miR.34a was significantly downregulated in AML patients[0.005(3.3×10^(-6)-1.32)],compared to the control subjects[0.108(3.2× 10^(-4)-1.64),p=0.021].The.median relative quantification(RQ)of miR-34a was 0.106(range;0-32.12).The specifaity,sensitivity,and area under the curve(AUC)for the diagnosis of AML were(58.3%,69.5%,0.707,respectively,p=0.021).patients with upregulated miR-34a showed decreased platelets count<34.5 × 10^(9)/L,and achieved early complete remission(CR,p=0.031,p=0.044,respectively).Similarly,patients who were refractory to therapy showed decreased miR 34a levels in comparison to those who achieved CR[0.002(0-0.01)and 0.12(0-32.12),respectively,p=0.002].Therefore,miR 34a could significantly identify patients with CR with a specificity of 75%and sensitivity of 100%at a cut-off of 0.014(AUC=0.927,p=0.005).There was no considerable association between miR-34a expression and survival rates of the induded AML patients.Condusion:miR-34a could be a beneficial diagnostic biomarker for AML patients.In addition,it serves as a good indicator for response to therapy,which could possibly identify patients who are refractory to treatment with 100%sensitivity and 75%specificity.

Clinical Effects of Venetoclax in the Treatment of Acute Myeloid Leukemia in the Elderly

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.

Observation on the Clinical Effect of Applying Venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

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.

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient evidence.This multicenter,randomized,phase 3 trial(ClinicalTrials.gov NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this study.Overall median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT group.Grade 3-4 adverse events(AEs)within two years posttransplantation in the two groups were similar.Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period posttransplantation.Haplo-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

Chidamide,Decitabine,Cytarabine,Aclarubicin,and Granulocyte Colony-stimulating Factor Therapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia:A Retrospective Study from a Single-Center

Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.

Myeloid sarcoma as the only manifestation in a rare mixed lineage leukemia-fusion-driven acute myeloid leukemia:A case report

BACKGROUND The mixed lineage leukemia(MLL)-eleven-nineteen lysine-rich leukemia(ELL)fusion gene is a rare occurrence among the various MLL fusion genes.We present the first case in which myeloid sarcoma(MS)was the only manifestation of adult MLL-ELL-positive acute myeloid leukemia(AML).CASE SUMMARY We report a case of a 33-year-old male patient who was admitted in June 2022 with a right occipital area mass measuring approximately 7 cm×8 cm.Blood work was normal.The patient underwent right occipital giant subscalp mass excision and incisional flap grafting.Immunohistochemistry was positive for myeloperoxidase,CD43 and CD45 and negative for CD3,CD20,CD34,and CD56.The bone marrow aspirate showed hypercellularity with 20%myeloblasts.Flow cytometry showed that myeloblasts accounted for 27.21%of the nucleated cells,which expressed CD33,CD38,and CD117.The karyotype was 46,XY,t(11,19)(q23;p13.1),-12,+mar/46,XY.Next-generation sequencing showed a fusion of MLL exon 7 to exon 2 of ELL.A diagnosis of MLL-ELL-positive AML(M2 subtype)with subcutaneous MS was made.CONCLUSION MLL-ELL-positive AML with MS is a rare clinical entity.Additional research is needed to elucidate the molecular mechanisms of the pathogenesis of MS.

T/myeloid mixed-phenotype acute leukemia treated with venetoclax and decitabine:A case report

BACKGROUND Mixed-phenotype acute leukemia(MPAL)is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid antigens.However,consensus regarding the ideal management strategy for MPAL is yet to be established,owing to its rarity.CASE SUMMARY A 55-year-old male was diagnosed with T/myeloid MPAL.Vincristine,prednisolone,daunorubicin,and L-asparaginase were administered as induction chemotherapy.Septic shock occurred 10 days after induction,and bone marrow examination following recovery from sepsis revealed refractory disease.Venetoclax and decitabine were administered as chemotherapy-free induction therapy to reduce the infection risk.There were no serious infections,including febrile neutropenia,at the end of the treatment.After receiving two additional cycles of venetoclax/decitabine,the patient underwent haploidentical peripheral blood stem-cell transplantation and achieved complete response(CR)to treatment.CONCLUSION CR was maintained in a patient with MPAL who underwent haploidentical peripheral blood stem-cell transplantation after additional venetoclax/decitabine cycles.

The Role of Mitochondrial VDAC2 in the Survival and Proliferation of T-Cell Acute Lymphoblastic Leukemia Cells

Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with aberrant T-cell developmental arrest. Individuals with relapsed T-ALL have limited therapeutic alternatives and poor prognosis. The mitochondrial function is critical for the T-cell viability. The voltage-dependent anion channel 2 (VDAC2) in the mitochondrial outer membrane, interacts with pro-apoptotic BCL-2 proteins and mediates the apoptosis of several cancer cell lines. Objective: The aim of the current study is to explore the role of VDAC2 in T-ALL cell survival and proliferation. Methods: Publicly available datasets of RNA-seq results were analyzed for expression of VDAC isoforms and T-ALL cell lines were treated with a VDAC2 small molecular inhibitor erastin. A VDAC2 RNA interference (siRNA) was delivered to T-ALL cell lines using a retroviral vector. Functional assays were performed to investigate the VDAC2 siRNA impacts on cell proliferation, apoptosis and survival of T-ALL cells. Results: Our analysis found a high expression of VDAC2 mRNA in various T-ALL cell lines. Public datasets of T-ALL RNA-seq also showed that VDAC2 is highly expressed in T-ALL (116.2 ± 36.7), compared to control groups. Only two T-ALL cell lines showed sensitivity to erastin (20 μM) after 48 hours of incubation, including Jurkat (IC50 = 3.943 μM) and Molt4 (IC50 = 3.286 μM), while another two T-ALL cells (CUTLL1 and RPMI 8402) had unstable IC50. However, five T-ALL cell lines (LOUCY, CCRF-CEM, P12-ICHI, HPB-ALL, and PEER cells) showed resistance to erastin. On the contrary, all T-ALL cell lines genetically inhibited with VDAC2 siRNA led to more than 80% decrease in VDAC2 mRNA levels, and a Conclusion: VDAC2 is highly expressed in T-ALL cells. The inhibition of VDAC2 significantly decreased cell viability, increased apoptosis, reduced cell proliferation and caused cell cycle sub-G1 arrest of T-ALL cells.

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.

Acute pancreatitis as initial presentation of acute myeloid leukemia-M2 subtype:A case report

BACKGROUND Direct infiltration of the pancreas by acute myeloid leukemia(AML)with acute pancreatitis(AP)as an initial symptom is extremely rare.Only once in the literature,the leukemia cells in AML have been implicated as the cause of AP.Pancreatitis caused by a rare predisposing factor is often misdiagnosed as idiopathic pancreatitis or pancreatitis of other common causes.Severe AP(SAP)progresses rapidly with a high fatality rate.Therefore,it is important to identify the predisposing factors in the early stage of SAP,evaluate the condition,determine prognosis,formulate treatment plans,and prevent a recurrence.Here,we describe a case of SAP due to AML.CASE SUMMARY A 61-year-old man presented to the hospital with fever and persistent abdominal pain.Blood analysis presented significantly elevated serum amylase and severe thrombocytopenia.Computed tomography examination of the abdomen revealed peripancreatic inflammatory effusion.The patient had no common etiologies and risk factors for AP,but the concurrent severe thrombocytopenia could not be explained by pancreatitis.Finally,the bone marrow aspirate and biopsy inspection revealed the underlying reason for pancreatitis,AML(M2 type based on the French-American-British classifications system).CONCLUSION Direct infiltration of the pancrease by acute leukemia,particularly AML cells,is an infrequent cause of AP.Therefore,although AP is a rare extramedullary infilt-ration characteristic for AML patients,it should be considered when determining the etiology of AP.

CD71-mediated liposomal arsenic-nickel complex combined with all-trans retinoic acid for the efficacy of acute promyelocytic leukemia

Clinically,arsenic trioxide(ATO)was applied to the treatment of acute promyelocytic leukemia(APL)as a reliable and effective frontline drug.However,the administration regimen of AsⅢwas limited due to its fast clearance,short therapeutic window and toxicity as well.Based on CD71 overexpressed on APL cells,in present study,a transferrin(Tf)-modified liposome(LP)was established firstly to encapsulate AsⅢin arsenic-nickel complex by nickel acetate gradient method.The AsⅢ-loaded liposomes(AsLP)exhibited the feature of acid-sensitive release in vitro.Tf-modified AsLP(Tf-AsLP)were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release AsⅢwhich stimulated reactive oxygen species level and caspase-3 activity.Tf-AsLP prolonged half-life of AsⅢin blood circulation,lowered systemic toxicity,and promoted apoptosis and induced cell differentiation at lesion site in vivo.Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect,accordingly,a Tf-modified RA liposome(Tf-RALP)was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy.As expected,the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model.Furthermore,APL orthotopic NOD/SCID mice model was established by 60CO irradiation and HL-60 cells intravenously injection.The effect of co-administration(Tf-AsLP+Tf-RALP)was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells’apoptosis and differentiation in peripheral blood and bone marrow.Collectively,Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug.Moreover,Tf-AsLP combined with Tf-RALP could achieve better efficacy.Thus,transferrinmodified AsⅢliposome would be a novel clinical strategy to improve patient compliance,with promising translation prospects.

A model based on eight iron metabolism-related genes accurately predicts acute myeloid leukemia prognosis

Purpose:Iron metabolism maintains the balance between iron absorption and excretion.Abnormal iron metabolism can cause numerous diseases,including tumor.This study determined the iron metabolism-related genes(IMRGs)signature that can predict the prognosis of acute myeloid leukemia(AML).The roles of these genes in the immune microenvironment were also explored.Methods:A total of 514 IMRGs were downloaded from the Molecular Characteristics Database(MSigDB).IMRGs related to AML prognosis were identified using Cox regression and LASSO analyses and were used to construct the risk score model.AML patients were stratified into high-risk groups(cluster 1)and low-risk groups(cluster 2)based on the mean value of the risk score.The accuracy and prognosis prediction potential of the risk-score model was evaluated using Kaplan-Meier and receiver operating characteristics analysis.The stromal score,immune scores,and immune cells infiltrated in AML samples were estimated using CIBERSORT,MCPcountre,and Xcell algorithms.The role of immune checkpoint genes in the AML microenvironment and the prognostic value of the IMRGs were also evaluated.Results:An AML prognosis prediction model was established based on the eight most critical IMRGs.Further analyses revealed that the model could accurately predict AML prognosis.The expression of IMRGs correlated with the infiltration of several immune cells and could influence response to certain chemotherapy drugs and immunotherapy.Conclusion:A model based on IMRGs can accurately predict the overall survival and disease-free survival of AML patients.

Expression and clinical significance of CANX in acute myeloid leukemia based on TCGA database

Objective:To explore relationships between CANX expression,prognosis and immune infiltration of acute myeloid leukemia(AML)patients.Methods:The TIMER database was used to compare the CANX expression among a variety of TCGA tumor and normal tissue samples.The difference of CANX expression between AML and normal samples was found by R software.The Kaplan-Meier method and Log-Rank test were used to assess the relationship between CANX expression and patient survival.The R software was used to find correlations between CANX expression,clinical characteristics,drug sensitivity,and immune infiltration in AML.Results:The differential expression of CANX in 13 tumor and normal tissue samples were statistically significant(P<0.05).The high CANX expression was associated with a favorable prognosis(P<0.05),which was validated in GSE37642.The expression of CANX was correlated with age,survival status,FAB stage,and karyotype(P<0.05).High CANX expression,low age and favorable karyotype were independent predictors of a favorable prognosis(P<0.05).CANX expression may affect the sensitivity of AML patients to multiple drugs(P<0.05).The expression of CANX was positively correlated with that of M1 macrophages and CD8 T cells.Conclusion:CANX may be used as a novel potential biomarker,and could benefit AML patients by predicting patient prognosis and providing precise treatment indications.