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First platelet transfusion refractoriness in a patient with acute myelocytic leukemia: A case report

World Journal of Clinical Cases 2023年第29期11卷 7156-7161页

作者： Sheng-Ke Tu Hong-Jie Fan Zi-Wei Shi Xiao-Lan Li Min Li Kui Song Department of Hematology The First Affiliated Hospital of Jishou UniversityJishou 416000Hunan ProvinceChina Department of Pharmacy The First Affiliated Hospital of Jishou UniversityJishou 416000Hunan ProvinceChina

BACKGROUND Platelet transfusion is of great significance in the treatment of thrombocytopenia caused by myelosuppression during intensive chemotherapy in patients with acute *** recent years,with platelet transfusion increasing,ineffective platelet transfusion has become increasingly *** speaking,platelet antibodies can be produced after repeated transfusion,thus rendering subsequent platelet transfusion *** 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 *** SUMMARY A 51-year-old female patient attended the hospital due to throat pain and abnormal blood cells for 4 *** 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)*** 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 *** 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 *** also suggests that we should consider the influence of antibiotics when the rare situation of first platelet transfusion failure occurs in patients with *** platelet antibodies are produced,immunoglobulins can be used to block antibodies,thereby reducing platelet *** 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.

关键词： acute myelocytic leukemia First platelet transfusion refractoriness Myelosuppression Nonimmune causes Immune-mediated causes Case report

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Amiodarone induces autophagy/mitophagy by activating sirtuin-3 in acute myelocytic leukemia

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中国药理学与毒理学杂志 2019年第10期 778-779页

作者： ZHANG Jin SUN De-juan ZHANG Lan OU Yang-liang State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University School of Life Science and Engineering Southwest Jiaotong University

OBJECTIVE To find a new treatment strategy foracute myelocytic leukemia(AML), we tried to find new targets. Sirtuin-3(SIRT3), a NAD+-dependent protein deacetylase localized primarily in the mitochondrion,is well-known to regulate autophagy, which is an evolutionarily conserved, multi-step lysosomal degradation process and also implicated in many diseases, such as *** evidence has revealed that SIRT3 may act as a tumor suppressor in AML, and thus activating SIRT3 will represent a potential therapeutic *** Aotophagy related protein expression and SIRT3 were analyzed by The Cancer Genome Atlas(TCGA)analysis. SIRT3 activator was selected by using in silico screening and anti-proliferative activities. The target selectivity of amiodarone was determined by co-crystal structure and deacetylase activity assays. The mechanisms of amiodarone-induced autophagy/mitophagy were investigated by fluorescence microscope, Western blotting, flow cytometry analysis, immunocytochemistry, as well as i TRAQ-based proteomics analysis. The therapeutic effect of amiodarone was assessed by xenograft AML mouse model. RESULTS TCGA dataset, we identified that SIRT3 was a key prognostic factor in AML, which was closely associated with the survival of patients. Subsequently, we computationally and experimentally screened a series of candidate activators of SIRT3 from Drugbank,and found the best candidate compound amiodarone,which was further validated by co-crystal structure of SIRT3/amiodarone. Interestingly, amiodarone induced autophagy via SIRT3-mediated AMPK-m TOR-ULK1-Beclin-1 pathway in U937 and HL-60 cells. Moreover,this activator induced mitophagy via SIRT3-deacetylating FOXO3 a and thus triggering PINK1/Parkin pathway in AML cells. The i TRAQ-based proteomics analyses revealed that amiodarone induced mitophagy by downregulating 14-3-3γ, upregulating and deacetylating Beclin-1,as well as activating FOXO3 a-HIF1α-BNIP3 and *** is more, deacetylation proteomics

关键词： amiodarone sirtuin-3 activator autophagy mitophagy acute myelocytic leukemia

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