Cancer Cell封面 白血病的关键基因

　　

生物通报道，加州大学医学院血液学与癌症研究部，Eli and Edythe Broad再生医学与干细胞研究中心，儿童医学系，生物学院干细胞研究中心等处的研究者发现了保护人类免受白血病的关键基因，这一成果以封面形式登上了Cancer Cell杂志，文章标题为：JunB Protects against Myeloid Malignancies by Limiting Hematopoietic Stem Cell Proliferation and Differentiation without Affecting Self-Renewal。

 

 

Emmanuelle等人研究发现缺失JunB/AP-1转录因子会诱导造血干细胞库产生骨髓组织增生性疾病（myeloproliferative disease ，MPD）。在本研究中，研究小组发现junB一旦失活会导致长效再生造血干细胞（long-term repopulating HSCs，LT-HSCs）复制周期和再生潜能不受管制。

 

研究者发现缺失JunB基因会导致细胞复杂的调控网络系统受到影响，多种信号通路出现紊乱，导致部分的转录因子功能异常，这些变化导致控制骨髓细胞分化的限制被解除，使得Notch和TGF-β信号通路中的Hes1基因的转录功能失效。

 

这些结果表明，长效再生造血干细胞（LT-HSCs）的增殖和分化功能与细胞自身的自我更新功能分裂，这一分裂骨髓祖细胞的再造限制被破坏，机体无法通过JunB系统限制骨髓细胞癌变。一旦JunB系统被破坏则导致白血病的发生，因此说研究者们找到了保护机体免受白血病的关键基因。

（生物通 小茜）

生物通推荐原文检索：JunB Protects against Myeloid Malignancies by Limiting Hematopoietic Stem Cell Proliferation and Differentiation without Affecting Self-Renewal。

【Summary】

Loss of the JunB/AP-1 transcription factor induces a myeloproliferative disease (MPD) arising from the hematopoietic stem cell (HSC) compartment. Here, we show that junB inactivation deregulates the cell-cycle machinery and increases the proliferation of long-term repopulating HSCs (LT-HSCs) without impairing their self-renewal or regenerative potential invivo. We found that JunB loss destabilizes a complex network of genes and pathways that normally limit myeloid differentiation, leading to impaired responsiveness to both Notch and TGF- signaling due in part to transcriptional deregulation of the Hes1 gene. These results demonstrate that LT-HSC proliferation and differentiation are uncoupled from self-renewal and establish some of the mechanisms by which JunB normally limits the production of myeloid progenitors, hence preventing initiation of myeloid malignancies.