Cell:重大发现!破坏白血病干细胞生物钟有望治疗白血病
来源:生物谷 2016-04-12 15:06
一项新研究发现急性骨髓性白血病干细胞不能够在缺乏它们内部的昼夜节律时存活下来。
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Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML
doi:10.1016/j.cell.2016.03.015
Rishi V. Puram, Monika S. Kowalczyk, Carl G. de Boer, Rebekka K. Schneider, Peter G. Miller, Marie McConkey, Zuzana Tothova, Héctor Tejero, Dirk Heckl, Marcus Järås, Michelle C. Chen, Hubo Li, Alfred Tamayo, Glenn S. Cowley, Orit Rozenblatt-Rosen, Fatima Al-Shahrour, Aviv Regev, Benjamin L. Ebert
Leukemia stem cells (LSCs) have the capacity to self-renew and propagate disease upon serial transplantation in animal models, and elimination of this cell population is required for curative therapies. Here, we describe a series of pooled, in vivo RNAi screens to identify essential transcription factors (TFs) in a murine model of acute myeloid leukemia (AML) with genetically and phenotypically defined LSCs. These screens reveal the heterodimeric, circadian rhythm TFs Clock and Bmal1 as genes required for the growth of AML cells in vitro and in vivo. Disruption of canonical circadian pathway components produces anti-leukemic effects, including impaired proliferation, enhanced myeloid differentiation, and depletion of LSCs. We find that both normal and malignant hematopoietic cells harbor an intact clock with robust circadian oscillations, and genetic knockout models reveal a leukemia-specific dependence on the pathway. Our findings establish a role for the core circadian clock genes in AML.
相关会议推荐
2016(第七届)细胞治疗国际研讨会
会议时间:2016.06.17-2016.06.18 会议地点:武汉
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