PDF(Pubmed)
Abstract：
Monosomy 7 and del(7q) are among the most common and poorly understood genetic alterations in myelodysplastic neoplasms and acute myeloid leukemia. Chromosome band 7q22 is a minimally deleted segment in myeloid malignancies with a del(7q). However, the rarity of \"second hit\" mutations supports the idea that del(7q22) represents a contiguous gene syndrome. We generated mice harboring a 1.5 Mb germline deletion of chromosome band 5G2 syntenic to human 7q22 that removes Cux1 and 27 additional genes. Hematopoiesis is perturbed in 5G2+/del mice but they do not spontaneously develop hematologic disease. Whereas alkylator exposure modestly accelerated tumor development, the 5G2 deletion did not cooperate with KrasG12D, NrasG12D, or the MOL4070LTR retrovirus in leukemogenesis. 5G2+/del mice are a novel platform for interrogating the role of hemopoietic stem cell attrition/stress, cooperating mutations, genotoxins, and inflammation in myeloid malignancies characterized by monosomy 7/del(7q).
摘要：
单体7和del（7q）是骨髓增生异常肿瘤和急性髓细胞性白血病中最常见且鲜为人知的遗传改变。染色体带7q22是骨髓性恶性肿瘤中带有del（7q）的最小缺失片段。然而,“二次命中”突变的罕见性支持了del（7q22）代表连续基因综合征的观点。我们产生了具有1.5Mb种系缺失的小鼠，其染色体带5G2与人7q22同源，从而去除Cux1和27个其他基因。5G2/del小鼠的造血功能受到干扰，但它们不会自发发展为血液病。而烷化剂暴露适度加速了肿瘤的发展，5G2删除与KrasG12D不合作，NrasG12D,或MOL4070LTR逆转录病毒在白血病发生。5G2+/del小鼠是询问造血干细胞损耗/应激作用的新平台，合作突变,基因毒素，以7/del（7q）为特征的髓系恶性肿瘤的炎症。
