用于研究MDS/AML转化机制及高通量药物筛选的斑马鱼白血病模型的建立

30%骨髓增生异常综合症(MDS)的病例可转变成急性白血病，这种转变又称为继发性急性髓系白血病(sAML或MDS/AML)。但目前尚缺乏一个可用于继发性白血病转化研究及高通量药物筛选的MDS/AML斑马鱼疾病模型。. c-MYB作为重要的转录因子参与髓系造血发育和分化过程，其过表达缺陷会导致人白血病。前期我们建立了一个c-myb过表达斑马鱼模型。总体表型类似人MDS，其中2%可转化为AML。转录因子 PU.1 是髓系白血病的抑制因子。在鼠和人类很多证据表明 PU.1 基因的低表达和前白血病的转化密切相关。本课题组前期研究发现在c-myb过表达的基础上降低pu.1的表达会出现AML的血液表型。本项目拟利用该双突变体建立可用于高通量药物筛选的MDS/AML斑马鱼疾病模型，阐明 MDS/AML的转化机制。

30% cases of Myelodysplastic syndrome (MDS) can transformed into acute leukemia, this transformation is also known as secondary acute myeloid leukemia (sAML or MDS/AML). However, there is still lacking a MDS/AML zebrafish disease model to study secondary leukemia transformation and high throughput drug screening.. C-MYB as important transcription factors involved in myeloid hematopoietic development and differentiation process. Defect of c-myb expression will lead to leukemia. In our previous studies, we set up a c-myb overexpression zebrafish model. The overall phenotype similar human MDS, 2% of which can be transformed into AML. Transcription factors PU.1 is myeloid leukemia inhibitory factor. There are a lot of evidence in mice and human, lower PU.1 expression is closely related to the transformation of the pre-leukemia . Our previous study found that,inhibit pu.1 level on the basis of c-myb overexpression pattern will induced AML. In this project,We intends to use the double mutant to establish MDS/AML zebrafish model for high throughput drug screening and the transformation mechanism of MDS/AML studying.