组蛋白乙酰转移酶p300/CBP在恶性肿瘤细胞中存在突变，组蛋白乙酰转移酶在骨髓增生异常综合征（MDS）到白血病转变过程的关键作用是目前国际上的研究热点。p300缺失能促进MDS到白血病的转化是我们在NUP98-HOXD13 (NHD13)转基因小鼠（模拟人MDS的小鼠模型）中发现的MDS转变为白血病的新机制。我们的研究显示敲除p300能增强NHD13小鼠骨髓造血干祖细胞自我更新能力并促进造血干细胞对称分裂；敲除p300还能促进NHD13小鼠造血干祖细胞的增殖，减少细胞凋亡。这些结果表明p300对MDS到白血病的转化致关重要。为了深入研究p300/CBP在MDS到白血病转变过程的作用及其机制，本课题组正在检测在NHD13小鼠中条件型敲除p300/CBP的表型，并将以此为研究对象，结合主要的细胞生物学、分子生物学和RNA测序技术阐明其作用机理，为其将来可能的临床应用提供重要依据。

The changes in histone acetylation play critical roles in the pathogenesis of human malignancies. It is a hot research area to study the key effect of histone acetyltransferase on the transformation of myelodysplastic syndrome (MDS) to AML. p300 and CBP, two distinct lysine acetyltransferases, are mutated in several cancers, suggesting their role as tumor suppressor genes. We found that deletion of p300, but not CBP, markedly accelerated the leukemogenesis of NUP98-HOXD13 (NHD13) transgenic mice, an animal model that phenotypically copies human MDS. p300 deletion restored the ability of NHD13 expressing bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) to self-renew in vitro, and to expand in vivo, with an increase in stem cell symmetric self-renewal divisions. p300 deletion also triggered increased proliferation and reduced apoptosis. To investigate the role of p300 in the the transformation of MDS to leukemia and the underlying mechanism, our lab is examining the effect of p300 deletion in the NHD13 transgenic MDS mouse model. We are also going to use the thechnolgies of cell biology, molecular biology and ChIP/RNA-seq to understand the mechanism of p300 deletion-induced transformation of MDS to leukemia. Altogether, our data will indicate that p300 plays a pivotal role in blocking the transformation of MDS to AML, which will provide the important basis for the potential therapeutic strategy in the clinical aspect.