Hu Tianyuan, Murdaugh Rebecca, Nakada Daisuke
Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, United States.
Program in Developmental Biology, Baylor College of Medicine, Houston, TX, United States.
Front Oncol. 2017 Nov 6;7:268. doi: 10.3389/fonc.2017.00268. eCollection 2017.
Leukemia is characterized by the uncontrolled production of leukemic cells and impaired normal hematopoiesis. Although the combination of chemotherapies and hematopoietic stem cell transplantation has significantly improved the outcome of leukemia patients, a proportion of patients still suffer from relapse after treatment. Upon relapse, a phenomenon termed "lineage switch" is observed in a subset of leukemia patients, in which conversion of lymphoblastic leukemia to myeloid leukemia or is observed. A rare entity of leukemia called mixed-phenotype acute leukemia exhibits co-expression of markers representing two or three lineages. These two phenotypes regarding the lineage ambiguity suggest that the fate of some leukemia retain or acquire a certain degree of plasticity. Studies using animal models provide insight into how lineage specifying transcription factors can enforce or convert a fate in hematopoietic cells. Modeling lineage conversion in normal hematopoietic progenitor cells may improve our current understanding of how lineage switch occurs in leukemia. In this review, we will summarize the role of transcription factors and microenvironmental signals that confer fate plasticity to normal hematopoietic progenitor cells, and their potential to regulate lineage switching in leukemias. Future efforts to uncover the mechanisms contributing to lineage conversion in both normal hematopoiesis and leukemia may pave the way to improve current therapeutic strategies.
白血病的特征是白血病细胞的失控产生以及正常造血功能受损。尽管化疗和造血干细胞移植的联合应用显著改善了白血病患者的治疗效果，但仍有一部分患者在治疗后会复发。复发时，在一部分白血病患者中会观察到一种称为“谱系转换”的现象，即会出现淋巴细胞白血病向髓细胞白血病的转化。一种罕见的白血病实体——混合表型急性白血病表现出代表两个或三个谱系的标志物的共表达。这两种关于谱系模糊性的表型表明，一些白血病的命运保留或获得了一定程度的可塑性。使用动物模型的研究有助于深入了解谱系特异性转录因子如何在造血细胞中强化或改变细胞命运。在正常造血祖细胞中模拟谱系转换可能会增进我们目前对白血病中谱系转换如何发生的理解。在这篇综述中，我们将总结赋予正常造血祖细胞命运可塑性的转录因子和微环境信号的作用，以及它们调节白血病谱系转换的潜力。未来揭示正常造血和白血病中谱系转换机制的努力可能为改进当前治疗策略铺平道路。
