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Consolidation Chemotherapy Prevents Relapse by Indirectly Regulating Bone Marrow Adipogenesis in Patients with Acute Myeloid Leukemia

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机构: [1]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Hematol, Shanghai, Peoples R China [2]Shanghai Jiao Tong Univ, Affiliated Tongren Hosp, Sch Med, Dept Hematol, Shanghai, Peoples R China [3]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Hematol, South Campus, Shanghai, Peoples R China [4]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 9, Sch Med, Dept Hematol, Shanghai, Peoples R China [5]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Blood Transfus, Shanghai, Peoples R China
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关键词: Acute myeloid leukaemia Bone marrow adipocytes Relapse Chemotherapy GDF15

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Background/Aims: Chemotherapy is still the main strategy used to prevent the relapse of acute myeloid leukaemia (AML). As the most abundant stromal component in bone marrow (BM), marrow adipocytes have been previously shown to promote leukaemogenesis. The present study was designed to further validate whether marrow adipocytes exert synergistic effects on strengthening chemotherapeutic efficacy and evaluate the underlying mechanism. Methods: A retrospective study of BM biopsies from 80 patients with AML in remission and 71 control subjects was applied to quantitatively analyse the marrow adipocyte volume. Toxicity tests were used to assess the effect of chemotherapy drugs on BM cells. The possible mechanisms by which chemotherapy regulated the reduced marrow adipocyte content were investigated using antibody neutralization experiments, with an emphasis on growth differentiation factor 15 (GDF15). Results: In our study, the marrow adipocyte content was obviously reduced in the AML-complete remission (CR) group compared with the control group (P<0.001). Moreover, patients with a reduced adipocyte content exhibited longer relapse-free survival (RFS) (P<0.001). We also confirmed that GDF15 was overexpressed in mononuclear cells (MNCs) after treatment with chemotherapy drugs and partially blocked mesenchymal stem cells (MSCs) adipogenesis. Intriguingly, this inhibitory effect on adipogenesis was rescued by treatment with a neutralizing anti-GDF15 antibody. Conclusion: Chemotherapy indirectly inhibited adipogenesis by promoting GDF15 secretion from BM MNCs, subsequently strengthening the efficacy of consolidation chemotherapy in patients with AML during CR. (C) 2018 The Author(s) Published by S. Karger AG, Basel

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出版当年[2017]版:
大类 | 2 区 生物
小类 | 2 区 生理学 3 区 细胞生物学
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出版当年[2016]版:
Q1 PHYSIOLOGY Q2 CELL BIOLOGY
最新[2023]版:
Q2 PHYSIOLOGY Q3 CELL BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2016版] 出版当年五年平均 出版前一年[2015版] 出版后一年[2017版]

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第一作者机构: [1]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Hematol, Shanghai, Peoples R China
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通讯机构: [1]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Hematol, Shanghai, Peoples R China [5]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Blood Transfus, Shanghai, Peoples R China [*1]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Hematol, Dept Blood Transfus, Shanghai, Peoples R China
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