Leukemia Propagating Cells Rebuild an Evolving Niche in Response to Therapy
Leukemia Propagating Cells Rebuild an Evolving Niche in Response to Therapy
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白血病增殖细胞根据治疗重建不断进化的生态位
DOI：
10.1016/j.ccr.2014.04.015
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发表时间：
2014-06-16
期刊：
影响因子：
50.3
通讯作者：
Hong, Deng-Li
中科院分区：
文献类型：
--
作者：
Duan, Cai-Wen;Shi, Jun;Hong, Deng-Li
肿瘤增殖细胞（cpc）在优先微环境生态位内的驻留是逃避治疗的主要原因。然而，所涉及的生态位的性质和保护cpc的机制在很大程度上仍然未知。我们在急性淋巴细胞白血病（ALL）的小鼠移植模型中解决了这些问题。当移植的白血病细胞严重破坏骨髓中邻近的微环境（BM）时，化疗后保留了小的CPCs灶，由支持细胞鞘包围，形成保护生态位。我们调查了患者的BM活检，并在接受诱导治疗的患者中发现了类似过程的证据。通过干扰小生境的形成或功能来提高化疗的疗效。因此，我们确定了一个治疗诱导的生态位来保护cpc。
Residence of cancer-propagating cells (CPCs) within preferential microenvironmental niches has a major part in evading therapy. However, the nature of niches involved and the mechanisms protecting CPCs remain largely unknown. We addressed these issues in mouse transplantation models of acute lymphoblastic leukemia (ALL). When the engrafted leukemic cells substantially damaged adjacent microenvironment in the bone marrow (BM), after chemotherapy small foci of CPCs were retained, surrounded by sheaths of supporting cells that comprise a protective niche. We investigated patients' BM biopsies and found evidence of a similar process in patients receiving induction therapy. The efficacy of chemotherapy was enhanced by interfering with the niche formation or function. We therefore identified a therapy-induced niche that protects CPCs.