Haploinsufficiency of Bcl11b for suppression of lymphomagenesis and thymocyte development
Haploinsufficiency of Bcl11b for suppression of lymphomagenesis and thymocyte development
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DOI：
10.1016/j.bbrc.2007.02.003
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发表时间：
2007-04-06
影响因子：
3.1
通讯作者：
Kominami, Ryo
中科院分区：
文献类型：
--
作者：
Kamimura, Kenya;Ohi, Hiroyuki;Kominami, Ryo
在BCL 11B处的复发性染色体重排发现于主要是T细胞起源的人类造血系统恶性肿瘤中。然而，目前还不清楚这种破坏如何有助于肿瘤发生，因为大多数白血病表达来自未破坏等位基因的BCL 11B。在这里，我们发现Bcl 11b（+/-）p53（+/-）小鼠比Bcl 11b（+/+）p53（+/-）小鼠对淋巴瘤表现出更大的易感性，但大多数淋巴瘤保留并表达野生型Bcl 11b等位基因。这有力地表明，Bcl 11 b单倍型不足以抑制p53（+/-）背景的小鼠胸腺淋巴瘤的发展，在这种情况下，只有一个等位基因的功能丧失赋予肿瘤生长的选择性优势。Bcl 11b（+/-）小鼠胚胎胸腺细胞发育和存活受损进一步支持了单倍不足。这些结果表明BCL 11 B畸变与人类白血病发生相关。(c)2007年爱思唯尔公司All rights reserved.
Recurrent chromosomal rearrangements at BCL11B are found in human hematopoietic malignancies mostly of T-cell origin. However, it is unclear how this disruption contributes to oncogenesis, because the majority of leukemias express BCL11B from an undisrupted allele. Here, we show that Bcl11b(+/-)p53(+/-) mice exhibited greater susceptibility to lymphomas than Bcl11b(+/+)p53(+/-) mice but most lymphomas retained and expressed the wild-type Bcl11b allele. This strongly suggests that Bcl11b is haplo insufficient for suppression of thymic lymphoma development in mice of the p53(+/-) background, a situation in which functional loss of only one allele confers a selective advantage for tumor growth. The haploinsufficiency is further supported by that Bcl11b(+/-) mouse embryos were impaired in thymocyte development and survival. These results indicate relevance of BCL11B aberration to human leukemogenesis. (c) 2007 Elsevier Inc. All rights reserved.