Hmga2 functions as an oncogene upon the deletion of Tet2 and promotes the pathogenesis of myelodysplastic syndrome.

High Mobility Group AT-hook 2 (HMGA2) has been found in a subset of patients with myeloid malignancies including myelodysplastic syndrome (MDS). Recent genome sequencing studies reveal the emergence of clonal hematopoiesis during aging as healthy aged people often harbor mutations of epigenetic modifiers including TET2 gene, which are often observed in MDS and myeloproliferative neoplasm (MPN) in patients. In order to understand how HMGA2 promotes the transformation of hematopoietic stem and progenitor cells, we generated a Hmga2-expressing Tet2-deficent mice model and explored the molecular mechanism of the pathogenesis of MDS.

研究已在包括骨髓增生异常综合征（myelodysplastic syndrome, MDS）在内的髓系恶性肿瘤患者亚群中检测到高迁移率族AT钩蛋白2（High Mobility Group AT-hook 2, HMGA2）的表达。近期基因组测序研究揭示，衰老过程中会出现克隆性造血现象：健康老年人常携带表观遗传调控因子（包括TET2基因）的突变，这类突变在骨髓增生异常综合征（MDS）与骨髓增殖性肿瘤（myeloproliferative neoplasm, MPN）患者中较为常见。为阐明HMGA2如何促进造血干祖细胞的恶性转化，本研究构建了过表达HMGA2且TET2缺陷的小鼠模型，并对骨髓增生异常综合征的发病分子机制进行了探究。