等位基因不平衡在骨髓增殖性肿瘤中的研究进展

在过去的5年间,一些研究已经提出了被称为经典骨髓增生性肿瘤(MPNs)的发病机制遗传学见解,首先是JAK2V617F基因突变的发现,然后是JAK2外显子12和MPLW515突变,这些发现修正了对这一疾病的理解、诊断和治疗。这些突变是导致这一疾病的致癌事件,然而,它们不能解释这些疾病发生的异质性。遗传缺陷在大约40%原发性血小板增多症和原发性骨髓纤维化疾病中仍未确定。另外,体遗传因素对MPNs表型同样重要,像目前提出的TET2、ASXL1和CBL基因突变。此外,JAK2基因多态性已经提出与MPNs相关。目前仍需要更深入地研究MPNs致癌的作用机制。

Research Advance of Allelic Imbalance in Myeloproliferative Tumor

During these past 5 years several studies have provided major genetic insights into the patho- genesis of the so-called classical myeloproliferative neoplasms （MPNs）. The discovery of the JAK2V617F mutation first, then of the JAK2 exon 12 and MPLW515 mutations, have modified the understanding, diagnois and management of the disease. These mutations are oncogenie events that cause the disorder;however,they do not explain the heterogeneity of the disease. Genetic defects have not been yet identified in around 40% of ET and PMF. There are likely additional somatic genetic factors important for the MPN phenotype like the recently described TET2, ASXL1, and CBL muta-tions. Moreover,palymorphisms in the JAK2 gene have been recently described as associated with MPNs. More studies are required for the carcinogenesis of MPNs.