PDF(Pubmed)
Abstract：
Adipocyte is a unique and versatile component of bone marrow microenvironment (BMM). However, the dynamic evolution of Bone Marrow (BM) adipocytes from the diagnosis of B cell Acute Lymphoblastic Leukemia (B-ALL) to the post-treatment state, and how they affect the progression of leukemia, remains inadequately explicated. Primary patient-derived xenograft models (PDXs) and stromal cell co-culture system are employed in this study. We show that the dynamic evolution of BM adipocytes from initial diagnosis of B-ALL to the post-chemotherapy phase, transitioning from cellular depletion in the initial leukemia niche to a fully restored state upon remission. Increased BM adipocytes retards engraftment of B-ALL cells in PDX models and inhibits cells growth of B-ALL in vitro. Mechanistically, the proliferation arrest of B-ALL cells in the context of adipocytes-enrichment niche, might attribute to the presence of adiponectin secreted by adipocytes themselves and the absence of cytokines secreted by mesenchymal stem cell (MSCs). In summary, our findings offer a novel perspective for further in-depth understanding of the dynamic balance between BMM and B-ALL.
摘要：
脂肪细胞是骨髓微环境（BMM）的独特且通用的组成部分。然而,骨髓（BM）脂肪细胞从B细胞急性淋巴细胞白血病（B-ALL）诊断到治疗后状态的动态演变，以及它们如何影响白血病的进展，仍然没有充分解释。在这项研究中采用了主要的患者来源的异种移植模型（PDX）和基质细胞共培养系统。我们显示BM脂肪细胞从B-ALL的初始诊断到化疗后阶段的动态演变，从最初的白血病小生境中的细胞耗竭过渡到缓解后的完全恢复状态。增加的BM脂肪细胞在PDX模型中延迟B-ALL细胞的植入并在体外抑制B-ALL的细胞生长。机械上,在脂肪细胞富集生态位的背景下，B-ALL细胞的增殖停滞，可能归因于脂肪细胞本身分泌的脂联素的存在和间充质干细胞（MSC）分泌的细胞因子的缺乏。总之,我们的研究结果为进一步深入理解BMM和B-ALL之间的动态平衡提供了新的视角.
