Donor cell leukemia: insight into cancer stem cells and the stem cell niche
Donor cell leukemia: insight into cancer stem cells and the stem cell niche
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DOI：
10.1182/blood-2006-07-021980
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发表时间：
2007-04-01
期刊：
影响因子：
20.3
通讯作者：
Kaufman, Dan S.
中科院分区：
文献类型：
--
作者：
Flynn, Catherine M.;Kaufman, Dan S.
供体细胞白血病（DCL）是造血细胞移植（HCT）中一种罕见的并发症。据报道，其发病率在0.12%至5%之间，尽管大多数病例是轶事。DCL的白血病发生机制可能不同于其他类型的白血病。DCL的可能原因包括免疫抑制者移植供体细胞的癌性改变或过早衰老。尽管最近许多研究已经更好地描述了白血病干细胞，但重要的是要考虑到造血微环境的内在细胞因子和外部信号控制着造血干细胞（hsc）的发育命运。因此，在DCL病例中，HCT后微环境的改变可能会增加正常造血干细胞的某些后代成为白血病的可能性。造血微环境中细胞、生长因子和细胞因子之间复杂的相互交流对于平衡造血干细胞自我更新、增殖和分化至关重要。然而，这种体内平衡可能在DCL的发展过程中受到干扰，从而对调节正常和潜在异常造血发育的刺激有了独特的见解。在这篇文章中，我们讨论了DCL的可能发病机制，它与干细胞的关系，以及它可能依赖于一个较少支持的干细胞生态位。
Donor cell leukemia (DCL) is a rare complication of hematopoietic cell transplantation (HCT). Its incidence has been reported between 0.12% and 5%, although the majority of cases are anecdotal. The mechanisms of leukemogenesis in DCL may be distinct from other types of leukemia. Possible causes of DCL include oncogenic alteration or premature aging of transplanted donor cells in an immunosuppressed person. Although many studies have recently better characterized leukemic stem cells, it is important to also consider that both intrinsic cell factors and external signals from the hematopoietic microenvironment govern the developmental fate of hematopoietic stem cells (HSCs). Therefore, in cases of DCL, alteration of the microenvironment after HCT may increase the likelihood that some progeny of normal HSCs become leukemic. This complex intercommunication between cells, growth factors, and cytokines in the hematopoietic microenvironment are critical to balance HSC self-renewal, proliferation, and differentiation. However, this homeostasis is likely perturbed in the development of DCL, allowing unique insight into the stimuli that regulate normal and potentially abnormal hematopoietic development. In this article, we discuss the possible pathogenesis of DCL, its association with stem cells, and its likely dependence on a less-supportive stem cell niche.