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首页> 外文期刊>Molecular and Cellular Biology >Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice.
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Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice.

机译：Meis1，一种与PBX1相关的同源盒基因，与BXH-2小鼠的髓样白血病有关。

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Leukemia results from the accumulation of multiple genetic alterations that disrupt the control mechanisms of normal growth and differentiation. The use of inbred mouse strains that develop leukemia has greatly facilitated the identification of genes that contribute to the neoplastic transformation of hematopoietic cells. BXH-2 mice develop myeloid leukemia as a result of the expression of an ecotropic murine leukemia virus that acts as an insertional mutagen to alter the expression of cellular proto-oncogenes. We report the isolation of a new locus, Meis1, that serves as a site of viral integration in 15% of the tumors arising in BXH-2 mice. Meis1 was mapped to a distinct location on proximal mouse chromosome 11, suggesting that it represents a novel locus. Analysis of somatic cell hybrids segregating human chromosomes allowed localization of MEIS1 to human chromosome 2p23-p12, in a region known to contain translocations found in human leukemias. Northern (RNA) blot analysis demonstrated that a Meis1 probe detected a 3.8-kb mRNA present in all BXH-2 tumors, whereas tumors containing integrations at the Meis1 locus expressed an additional truncated transcript. A Meis1 cDNA clone that encoded a novel member of the homeobox gene family was identified. The homeodomain of Meis1 is most closely related to those of the PBX/exd family of homeobox protein-encoding genes, suggesting that Meis1 functions in a similar fashion by cooperative binding to a distinct subset of HOX proteins. Collectively, these results indicate that altered expression of the homeobox gene Meis1 may be one of the events that lead to tumor formation in BXH-2 mice.
机译：白血病是由于多种遗传变异的积累而破坏了正常生长和分化的控制机制。发生白血病的近交小鼠品系的使用极大地促进了鉴定有助于造血细胞肿瘤转化的基因。 BXH-2小鼠由于嗜好性鼠白血病病毒的表达而发展成髓性白血病，该易性鼠白血病病毒可作为插入诱变剂来改变细胞原癌基因的表达。我们报告了一个新的基因位点，Meis1的隔离，该位点是BXH-2小鼠中15％的肿瘤中病毒整合的一个位点。 Meis1被映射到小鼠近端11号染色体上的不同位置，表明它代表了一个新的基因座。分离人类染色体的体细胞杂种的分析允许将MEIS1定位于人类染色体2p23-p12，该区域位于已知包含人类白血病中易位的区域。 Northern（RNA）印迹分析表明，Meis1探针检测到存在于所有BXH-2肿瘤中的3.8-kb mRNA，而在Meis1基因座处整合的肿瘤表达了另一条截短的转录本。一个Meis1 cDNA克隆编码了同源盒基因家族的一个新成员被确定。 Meis1的同源域与同源盒蛋白编码基因的PBX / exd家族的亲缘域最紧密相关，这表明Meis1通过与HOX蛋白的不同子集协同结合以相似的方式发挥功能。总体而言，这些结果表明，同源盒基因Meis1的表达改变可能是导致BXH-2小鼠肿瘤形成的事件之一。

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