Role of Cbfb in hematopoiesis and perturbations resulting from expression of the leukemogenic fusion gene Cbfb-MYH11
Role of Cbfb in hematopoiesis and perturbations resulting from expression of the leukemogenic fusion gene Cbfb-MYH11
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DOI：
10.1182/blood-2002-04-1064
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发表时间：
2002-10-01
期刊：
影响因子：
20.3
通讯作者：
Liu, PP
中科院分区：
文献类型：
--
作者：
Kundu, M;Chen, A;Liu, PP
核心致盲因子β(CBFbeta)和CBFalpha2形成异源二聚体转录因子，在造血过程中发挥重要作用。在超过30%的急性髓系白血病(AML)患者中，编码CBFbeta或CBFalpha2的基因参与了染色体重排，提示CBFbeta和CBFalpha2在白血病发生中起重要作用。Inv(16)(p13；q22)在几乎所有的AML M4Eo病例中都存在，并导致CBFbeta与编码平滑肌肌球蛋白重链的基因MYH11融合。Cbfb-MYH11敲入基因杂合子的小鼠胚胎缺乏明确的造血功能，这是Cbfb(-/-)胚胎共有的一种表型。在这项研究中，我们建立了Cbfb-GFP敲入小鼠模型，以表征Cbfbeta在造血细胞中的正常表达模式。在中期胚胎中，Cbfbeta在造血干细胞和祖细胞丰富的群体中表达。在Cbfb-MYH11敲入基因杂合子的小鼠胚胎中不存在这种干细胞和祖细胞群体。总之，这些数据表明Cbfb-MYH11在干祖细胞水平上阻止了胚胎的造血，并且Cbfb对于造血干细胞和祖细胞的产生是必不可少的。在成年小鼠中，Cbfbeta在干细胞和祖细胞以及成熟的髓细胞和淋巴样细胞中表达。虽然Cbfβ在红系祖细胞中表达，但在红系生成的末期不表达。我们的数据表明Cbfb是髓系和淋巴系分化所必需的，但在红系分化中不起关键作用。2002年由美国血液病学会公布。
Core-blinding factor beta (CBFbeta) and CBFalpha2 form a heterodimeric transcription factor that plays an important role in hematopoiesis. The genes encoding either CBFbeta or CBFalpha2 are involved in chromosomal rearrangements In more than 30% of cases of acute myeloid leukemia (AML), suggesting that CBFbeta and CBFalpha2 play important roles in leukemogenesis. Inv(16)(p13; q22) is found in almost all cases of AML M4Eo and results in the fusion of CBFbeta with MYH11, the gene encoding smooth muscle myosin heavy chain. Mouse embryos heterozygous for a Cbfb-MYH11 knock-in gene lack definitive hematopoiesis, a phenotype shared by Cbfb(-/-) embryos. In this study we generated a Cbfb-GFP knock-in mouse model to characterize the normal expression pattern of Cbfbeta in hematopoietic cells. In midgestation embryos, Cbfbeta was expressed in populations enriched for hematopoietic stem cells and progenitors. This population of stem cells and progenitors was not present in mouse embryos heterozygous for the Cbfb-MYH11 knock-in gene. Together, these data suggest that Cbfb-MYH11 blocks embryonic hematopoiesis at the stem-progenitor cell level and that Cbfb is essential for the generation of hematopoietic stem and progenitor cells. In adult mice, Cbfbeta was expressed in stem and progenitor cells, as well as mature myelold and lymphoid cells. Although it was expressed in erythroid progenitors, Cbfbeta was not expressed during the terminal stages of erythropoiesis. Our data indicate that Cbfb is required for myeloid and lymphoid differentiation; but does not play a critical role in erythroid differentiation. 2002 by The American Society of Hematology.