Meyer Lauren K, Hermiston Michelle L
Department of Pediatrics, University of California, San Francisco, SF 94158, USA.
Cancer Drug Resist. 2019 Dec 19;2(4):1164-1177. doi: 10.20517/cdr.2019.63. eCollection 2019.
Acute lymphoblastic leukemia (ALL) is a malignancy of immature lymphoid cells that arises due to clonal expansion of cells that undergo developmental arrest and acquisition of pathogenic mutations. With the introduction of intensive multi-agent chemotherapeutic regimens, survival rates for ALL have improved dramatically over the past several decades, though survival rates for adult ALL continue to lag behind those of pediatric ALL. Resistance to chemotherapy remains a significant obstacle in the treatment of ALL, and chemoresistance due to molecular alterations within ALL cells have been described. In addition to these cell-intrinsic factors, the bone marrow microenvironment has more recently been appreciated as a cell-extrinsic mediator of chemoresistance, and it is now known that stromal cells within the bone marrow microenvironment, through direct cell-cell interactions and through the release of lymphoid-acting soluble factors, contribute to ALL pathogenesis and chemoresistance. This review discusses mechanisms of chemoresistance mediated by factors within the bone marrow microenvironment and highlights novel therapeutic strategies that have been investigated to overcome chemoresistance in this context.
急性淋巴细胞白血病（ALL）是一种未成熟淋巴细胞的恶性肿瘤，它是由于经历发育停滞并获得致病突变的细胞发生克隆性扩增而产生的。随着强化多药化疗方案的引入，在过去几十年中ALL的生存率有了显著提高，尽管成人ALL的生存率仍落后于儿童ALL。化疗耐药仍然是ALL治疗中的一个重大障碍，并且已经描述了ALL细胞内分子改变导致的化疗耐药。除了这些细胞内在因素外，骨髓微环境最近被认为是化疗耐药的细胞外在介导因素，现在已知骨髓微环境中的基质细胞通过直接的细胞间相互作用以及通过释放具有淋巴细胞作用的可溶性因子，促进ALL的发病机制和化疗耐药。本综述讨论了由骨髓微环境中的因素介导的化疗耐药机制，并强调了在此背景下为克服化疗耐药而研究的新治疗策略。
