Jia Xi, Liao Naying, Yao Yunqian, Guo Xutao, Chen Kai, Shi Pengcheng
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
Department of Radiotherapy, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Cancer Biol Ther. 2024 Dec 31;25(1):2323765. doi: 10.1080/15384047.2024.2323765. Epub 2024 Mar 11.
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.
脂肪细胞是骨髓微环境(BMM)中一种独特且多功能的成分。然而,从B细胞急性淋巴细胞白血病(B-ALL)诊断到治疗后状态,骨髓(BM)脂肪细胞的动态演变以及它们如何影响白血病的进展,仍未得到充分阐释。本研究采用了原发性患者来源的异种移植模型(PDXs)和基质细胞共培养系统。我们发现,BM脂肪细胞从B-ALL初始诊断到化疗后阶段的动态演变,是从初始白血病龛中的细胞耗竭转变为缓解时的完全恢复状态。BM脂肪细胞增加会延缓PDX模型中B-ALL细胞的植入,并在体外抑制B-ALL细胞的生长。从机制上讲,在富含脂肪细胞的龛环境中B-ALL细胞的增殖停滞,可能归因于脂肪细胞自身分泌的脂联素的存在以及间充质干细胞(MSCs)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与B-ALL之间的动态平衡提供了新的视角。