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Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report
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作者 Fu-Yu Yang Lei Shao +1 位作者 Jie Su Zhen-Meng Zhang 《World Journal of Clinical Cases》 SCIE 2024年第3期623-629,共7页
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
关键词 Carrimycin Hematologic disease acute myeloid leukemia acute promyelocytic leukemia Pulmonary tuberculosis Case report
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Adult rhabdomyosarcoma combined with acute myeloid leukemia: A case report
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作者 Lu Zheng Fen-Juan Zhang 《World Journal of Clinical Cases》 SCIE 2024年第3期582-586,共5页
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... 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. 展开更多
关键词 RHABDOMYOSARCOMA Secondary acute myeloid leukocytes CHEMOTHERAPEUTICS Secondary leukemia Case report
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Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia
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作者 Zhen LU Qian LAI +8 位作者 Zhi-feng LI Meng-ya ZHONG Yue-long JIANG Li-ying FENG Jie ZHA Jing-wei YAO Yin LI Xian-ming DENG Bing XU 《Current Medical Science》 SCIE CAS 2024年第2期298-308,共11页
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 r... 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. 展开更多
关键词 B-cell acute lymphoblastic leukemia dual-target inhibitor NF-KB c-Myc PI3K/AKT p53
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Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis 被引量:1
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作者 Jiaqi Tang Lin Luo +18 位作者 Bakwatanisa Bosco Ning Li Bin Huang Rongrong Wu Zihan Lin Ming Hong Wenjie Liu Lingxiang Wu Wei Wu Mengyan Zhu Quanzhong Liu Peng Xia Miao Yu Diru Yao Sali Lv Ruohan Zhang Wentao Liu Qianghu Wang Kening Li 《Journal of Biomedical Research》 CAS CSCD 2024年第4期397-412,共16页
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
关键词 acute myeloid leukemia cell surface markers PROGNOSIS drug sensitivity multi-model analysis
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Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia
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作者 Tong-yuan LIU Xing FU +3 位作者 Ying YANG Jia GU Min XIAO Deng-ju LI 《Current Medical Science》 SCIE CAS 2024年第4期799-808,共10页
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
关键词 GLUTAMINE METFORMIN acute myeloid leukemia METALLOTHIONEIN
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Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis
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作者 Ying CHEN Bi-xia LI +9 位作者 Ting-ting NIU Shu-jun YANG Li-chao WU Le-huai SHI Duo-bing ZOU Ning-ning WU Li-xia SHENG Xiao YAN Gui-fang OUYANG Qi-tian MU 《Current Medical Science》 SCIE CAS 2024年第3期611-622,共12页
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
关键词 acute myeloid leukemia circ_0012152 miR-652-3p SOX4 cell growth
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Damage Mechanism of CK2 and IKAROS in Philadelphia Like Acute Lymphoblastic Leukemia
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作者 Ignacio Vélez-Rodríguez Victoria Carranza-Aranda 《Journal of Biosciences and Medicines》 2024年第4期49-59,共11页
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 lym... 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). 展开更多
关键词 acute Lymphoblastic leukemia IKAROS DEPHOSPHORYLATION Philadelphia Chromosome CK2
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Incidence and Survivability of Acute Lymphocytic Leukemia Patients in the United States: Analysis of SEER Data Set from 2000-2019
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作者 Ishan Ghosh Sudipto Mukherjee 《Journal of Cancer Therapy》 2024年第4期141-163,共23页
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 takin... 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. 展开更多
关键词 acute Lymphocytic leukemia SURVIVABILITY INCIDENCE DEMOGRAPHY SEER Data Set
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Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis
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作者 Wan Li Sheng-Yu Ma Hui-Ying Zhao 《World Journal of Clinical Cases》 SCIE 2024年第20期4121-4129,共9页
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
关键词 acute myeloid leukemia Transforming growth factor-β1 Vascular endothelial growth factor Expression level Prognostic correlation
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Clinical Effects of Venetoclax in the Treatment of Acute Myeloid Leukemia in the Elderly
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作者 Ben Niu Limin Hou 《Proceedings of Anticancer Research》 2024年第3期80-83,共4页
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
关键词 Venetoclax ELDERLY acute myeloid leukemia EFFICACY
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Observation on the Clinical Effect of Applying Venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia
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作者 Ben Niu Limin Hou 《Journal of Clinical and Nursing Research》 2024年第4期248-252,共5页
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
关键词 acute myeloid leukemia Venetoclax Demethylating drugs Combination therapy EFFICACY
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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
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作者 Fan-cong KONG Ling QI +3 位作者 Yu-lan ZHOU Min YU Wen-feng HUANG Fei LI 《Current Medical Science》 SCIE CAS 2023年第6期1151-1161,共11页
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 ... 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. 展开更多
关键词 relapsed/refractory acute myeloid leukemia histone deacetylase inhibitor DNA methyltransferase inhibitor salvage therapy
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The Role of Mitochondrial VDAC2 in the Survival and Proliferation of T-Cell Acute Lymphoblastic Leukemia Cells
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作者 Filippus Iipinge Tshavuka Lin Zou 《Journal of Biosciences and Medicines》 2023年第10期265-283,共19页
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 po... 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 (IC<sub>50</sub> = 3.943 μM) and Molt4 (IC<sub>50</sub> = 3.286 μM), while another two T-ALL cells (CUTLL1 and RPMI 8402) had unstable IC<sub>50</sub>. 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. 展开更多
关键词 VDAC2 Mitochondrial-Mediated Apoptosis T-Cell acute Lymphoblastic leukemia
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Myeloid sarcoma as the only manifestation in a rare mixed lineage leukemia-fusion-driven acute myeloid leukemia:A case report
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作者 Sheng-Jie Tang Qi-Guo Zhang 《World Journal of Clinical Cases》 SCIE 2023年第25期6000-6004,共5页
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 onl... 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. 展开更多
关键词 Myeloid sarcoma acute myeloid leukemia Mixed lineage leukemia-elevennineteen lysine-rich leukemia TRANSPLANTATION Case report
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T/myeloid mixed-phenotype acute leukemia treated with venetoclax and decitabine:A case report
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作者 Sungwoo Park Eun Jeong Jeong +4 位作者 Jung Hun Kang Gyeong-Won Lee Se-Il Go Dong-Hyun Lee Eun-Ha Koh 《World Journal of Clinical Cases》 SCIE 2023年第26期6200-6205,共6页
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 ... 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. 展开更多
关键词 Mixed-phenotype acute leukemia Venetoclax DECITABINE Case report
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First platelet transfusion refractoriness in a patient with acute myelocytic leukemia: A case report 被引量:1
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作者 Sheng-Ke Tu Hong-Jie Fan +3 位作者 Zi-Wei Shi Xiao-Lan Li Min Li Kui Song 《World Journal of Clinical Cases》 SCIE 2023年第29期7156-7161,共6页
BACKGROUND Platelet transfusion is of great significance in the treatment of thrombocytopenia caused by myelosuppression during intensive chemotherapy in patients with acute leukemia.In recent years,with platelet tran... BACKGROUND Platelet transfusion is of great significance in the treatment of thrombocytopenia caused by myelosuppression during intensive chemotherapy in patients with acute leukemia.In recent years,with platelet transfusion increasing,ineffective platelet transfusion has become increasingly prominent.Generally speaking,platelet antibodies can be produced after repeated transfusion,thus rendering subsequent platelet transfusion ineffective.We report a case of first platelet transfusion refractoriness(PTR)in a patient with acute myelocytic leukemia(AML).Due to the rarity of such cases in clinical practice,there have been no relevant case reports so far.CASE SUMMARY A 51-year-old female patient attended the hospital due to throat pain and abnormal blood cells for 4 d.Her diagnosis was acute myelocytic leukemia[M2 type Fms related receptor tyrosine kinase 3,Isocitrate Dehydrogenase 1,Nucleophosmin 1,Neuroblastoma RAS viral oncogene homolog(+)high-risk group].She was treated with"IA"(IDA 10 mg day 1-3 and Ara-C 0.2 g day 1-5)chemotherapy.When her condition improved,the patient was discharged from the hospital,instructed to take medicine as prescribed by the doctor after discharge,and returned to the hospital for further chemotherapy on time.CONCLUSION We report a rare case of first platelet transfusion failure in a patient with AML during induction chemotherapy,which may be related to the production of platelet antibodies induced by antibiotics and excessive tumor load.This also suggests that we should consider the influence of antibiotics when the rare situation of first platelet transfusion failure occurs in patients with AML.When platelet antibodies are produced,immunoglobulins can be used to block antibodies,thereby reducing platelet destruction.For patients with PTR,both immune and non-immune factors need to be considered and combined in clinical practice along with individualized treatment to effectively solve the problem. 展开更多
关键词 acute myelocytic leukemia First platelet transfusion refractoriness MYELOSUPPRESSION Nonimmune causes Immune-mediated causes Case report
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Acute pancreatitis as initial presentation of acute myeloid leukemia-M2 subtype:A case report
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作者 Wen-Xin Yang Kang An +2 位作者 Gai-Fang Liu Heng-Yu Zhou Jun-Cha Gao 《World Journal of Clinical Cases》 SCIE 2023年第6期1385-1392,共8页
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 implicate... 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. 展开更多
关键词 acute pancreatitis acute myeloid leukemia Abdominal pain Extramedullary infiltration ETIOLOGY Case report
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CD71-mediated liposomal arsenic-nickel complex combined with all-trans retinoic acid for the efficacy of acute promyelocytic leukemia
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作者 Xiao Liu Lili Zhang +7 位作者 Yueying Yang Weiwei Yin Yunhu Liu Chunyi Luo Ruizhe Zhang Zhiguo Long Yanyan Jiang Bing Wang 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2023年第4期80-95,共16页
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 clearan... 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. 展开更多
关键词 TRANSFERRIN Arsenic trioxide acute promyelocytic leukemia All-trans retinoic acid LIPOSOME
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A model based on eight iron metabolism-related genes accurately predicts acute myeloid leukemia prognosis
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作者 ZHANSHU LIU XI HUANG 《BIOCELL》 SCIE 2023年第3期593-605,共13页
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)si... 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. 展开更多
关键词 acute myeloid leukemia IMRGs Prognostic signature Infiltrating immune cells BIOINFORMATICS
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Expression and clinical significance of CANX in acute myeloid leukemia based on TCGA database
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作者 LI Bo-ya LI Tong +2 位作者 ZU Xiang-yang WANG Chong QIN Ling 《Journal of Hainan Medical University》 CAS 2023年第5期53-60,共8页
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... 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. 展开更多
关键词 CANX acute myeloid leukemia PROGNOSIS Immune cell BIOMARKER
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