Nakamura T, Largaespada D A, Shaughnessy J D, Jenkins N A, Copeland N G
Mammalian Genetics Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Nat Genet. 1996 Feb;12(2):149-53. doi: 10.1038/ng0296-149.
Retroviruses induce myeloid leukaemia in BXH-2 mice by the insertional mutation of cellular proto-oncogenes or tumour suppressor genes. Disease genes can thus be identified by proviral tagging through the identification of common viral integration sites in BXH-2 leukaemia. Here, we describe a new approach for proviral tagging that greatly facilitates the identification of BXH-2 leukaemia genes. Using this approach, we identify three genes whose expression is activated by proviral integration in BXH-2 leukaemias; Hoxa7, Hoxa9, and a Pbx1-related homeobox gene, Meis1. Proviral activation of Hoxa7 or Hoxa9 is strongly correlated with proviral activation of Meis1 implying that Hoxa7 and Hoxa9 cooperate with Meis1 in leukaemia formation. These studies provide the first genetic evidence that Pbx1-related genes cooperate with Hox genes in leukaemia formation and identify a number of new murine myeloid leukaemia genes.
逆转录病毒通过细胞原癌基因或肿瘤抑制基因的插入突变在BXH-2小鼠中诱发髓系白血病。因此，通过在BXH-2白血病中鉴定常见的病毒整合位点进行前病毒标签，可以识别疾病基因。在此，我们描述了一种新的前病毒标签方法，该方法极大地促进了BXH-2白血病基因的鉴定。使用这种方法，我们鉴定了三个基因，其表达在BXH-2白血病中被前病毒整合激活；Hoxa7、Hoxa9和一个与Pbx1相关的同源盒基因Meis1。Hoxa7或Hoxa9的前病毒激活与Meis1的前病毒激活密切相关，这意味着Hoxa7和Hoxa9在白血病形成过程中与Meis1协同作用。这些研究提供了首个遗传学证据，表明与Pbx1相关的基因在白血病形成过程中与Hox基因协同作用，并鉴定了一些新的小鼠髓系白血病基因。
