Cell：拆穿癌症干细胞的伪装

　　

生物通报道，斯坦福大学病理系，表观遗传学系及英国曼彻斯特大学癌症研究中心的科学家们在Cell旗下的Cell Stem Cell上发表最新文章，揭开白血病干细胞（癌症干细胞的一种）的伪装，研究发现相比成体干细胞，白血病干细胞更具有胚胎干细胞的特征。

 

在急性髓细胞样白血病发生过程中，白血球过多症干细胞（leukemia stem cells，简称LSCs）维持其多能性的遗传调控网络一直是个谜。现在，研究者们通过AML（急性髓细胞样白血病）小鼠模型研究这一机制。

 

研究结果表明，LSCs的多能性与其致癌基因有极大的关联，其与胚胎干细胞一样具有一个转录的子程序以维持其自我更新的能力。在这个转录体系中，转录因子Myb，Hmgb3和Cbx5起关键的作用，其中HoxaMeis系统也独立地共表达使得LSCs具有无限的增殖能力，这有助LSCs保持与胚胎干细胞一样的性能与之共享相同的转录体系。往往这一结果会导致癌症干细胞获得无限制的自我更新能力，往往导致癌症患者预后不良。（生物通 小茜）

 

生物通推荐原文检索：Hierarchical Maintenance of MLL Myeloid Leukemia Stem Cells Employs a Transcriptional Program Shared with Embryonic Rather Than Adult Stem Cells

 

目前该文章为Cell Stem Cell的特刊文章，可获得免费全文。

链接地址：http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(08)00617-6

 

【Summary】

The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional subprogram more akin to that of embryonic stem cells (ESCs) than to that of adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3, and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when coexpressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia-initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor-prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells (CSCs) to prognosis in human cancer.（生物通）