慢性粒细胞白血病bcr-abl基因相关的频繁杂合性丢失(英文)

bcr-abl融合基因是慢性粒细胞白血病(CML)慢性期唯一特征性分子标志,但目前对于bcr-abl外的遗传事件在CML发生中的作用所知甚少。杂合性丢失(LOH)是肿瘤基因组中抑癌基因(TSG)失活的信号,是癌发生普遍而重要的遗传机制之一。评价LOH在CML中的改变以及它们同CML的特征性分子标志bcr-abl融合基因的关系,对于阐明CML的发病机制具有重要意义。本实验研究使用以PCR为基础的微卫星多态分型分析了同CML的分子标志bcr-abl融合基因相关的LOH。通过扩增位于abl基因座位附近的微卫星标志D9S66座位的(CA)n双核苷酸简单重复序列,研究了一组CML中的微卫星改变。在21例CML慢性期、加速期和急变期病人中共发现8例有频繁的LOH;相反,无1例表现出类似遗传性非腺瘤病性结肠癌(HNPCC)所有的微卫星不稳定性。研究结果提示,LOH是CML中的一个重要事件,可能涉及在CML发生中abl基因座位附近的TSG的失活或丢失。

Frequent Loss of Heterozygosity Associated with bcr-abl Gene in Chronic Myeloid Leukemia

Loss of heterozygosity (LOH) associated with the hallmark of pathogenesis of chronic myeloid leukemia (CML), the bcr-abl fusion gene, has not yet been systematically analyzed by microsatellite assays. The microsatellite marker D9S66 in the vicinity of locus of abl gene was used to investigate the microsatellite alterations in a variety of chronic myeloid leukemias based on PCR methods. Frequent LOHs were detected in 8 of total 21 CML patients in chronic, accelerated, and blastic phases. In contrast, no one manifested the microsatellite instabilities resembling those in hereditary non-polvposis colorectal carcinoma (HNPCC). Our results argue that LOH is an important event in CML and the inactivation or loss of a possible tumor sup-pressor gene may be involved in the leukemogenesis of CML.