IKZF1/PFAS融合基因在BPDCN及其向AML演进中的作用及机制研究

母细胞性浆细胞样树突细胞肿瘤(BPDCN)是起源于浆细胞样树突细胞（pDCs）的高度侵袭性髓系肿瘤，常发展为急性髓系白血病（AML）。我们前期在BPDCN患者中发现并克隆了一种新的融合基因IKZF1/PFAS，转染至iPSCs细胞系, 发现其改变向CD31+CD43+祖细胞定向分化过程中CD分子表型及成克隆能力，参与调节诱导多能干细胞（iPSCs）定向分化。由此，本课题组拟进一步向髓系祖细胞及pDCs两个方向继续定向分化，从形态学、免疫表型、细胞免疫功能、细胞生物学行为四个层面探索IKZF1/PFAS在BPDCN-AML的作用，采用转录组学和小分子抑制剂阻断分析该融合基因通过TGF-β1信号通路导致BPDCN/AML的发生的机制；同时构建IKZF1/PFAS敲入鼠模型，观察肿瘤形成及体内验证致病机制。

blastic plasmacytoid dendritic cell neoplasm（BPDCN）is an invasiv myeloid neoplasm orignated from Plasmacytoid dendritic cells（pDCs）, which usually develope to Acute myeloid leukemia (AML). We detected a novel fusion gene-IKZF1/PFAS in BPDCN, the IKZF1/PFAS positive induced pluripotent stem cells (iPSCs) has diffenrent CD marker expression and clone formation, comfirm its effect in directional differentiation. Based on this, we will explore the morphology, immuology, secretion function, cell biological behavior, transcriptomics in transforming growth factorβ1(TGF-β1) in myeloid and pDCs differentiation directions in future work, thus reveal the pathogenesis on IKZF1/PFAS in BPDCN and AML evolution. At the same time, IKZF1/PFAS transgenic mice model will be used to observe the tumor formation and comfirm the mechnism of pathogenesis in vitro.