Analysis of regulatory mechanism of hematopoiesis and exploration of the pathogenesis of hematopoietic neoplasms through comprehensive genetic analysis

造血肿瘤是由基因突变引起的造血系统正常成分的失调引起的。事实上，许多被确认为造血肿瘤原因的基因变化涉及到那些与正常的造血调控有关的基因。在这项研究中，我们使用高密度SNP阵列对2000多种血液肿瘤进行了全面的遗传分析。我们确定了一些与造血肿瘤发病相关的基因改变，包括髓系肿瘤中c-CBL的功能获得突变和B系淋巴瘤中A20的失活突变，并对它们进行了功能分析。这些发现不仅有助于我们理解血液病的分子发病机制，而且有助于增加我们对正常造血调控机制的认识，以及开发针对这些肿瘤的新的诊断和治疗方法。

Hematopoietic neoplasms are caused by deregulation of normal components of the hematopoietic system by gene mutations. In fact, many of genetic changes identified as a cause of hematopoietic neoplasms involves those genes implicated in normal regulation of hematopoiesis. In this study, we performed comprehensive genetic analyses of more than 2,000 hematopoietic neoplasms using high-density SNP arrays. We identified a number of genetic alterations involved in the pathogenesis of hematopoietic neoplasms, including gain-of-function mutations of c-CBL in myeloid neoplasms and inactivation mutations of A20 in B-lineage lymphomas, followed by their functional analysis. These findings are thought to contribute not only to our understanding of molecular pathogenesis of hematopoietic cancers, but also to adding our knowledge on regulatory mechanisms of normal hematopoiesis, together with the development of novel diagnostics and therapeutics for these neoplasms.