Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia [Chip-Seq]

The caudal-related homeobox transcription factor CDX2 is ectopically expressed in the majority of patients with acute myeloid leukemia (AML). We generated an inducible transgenic mouse model whereby Cdx2 was specifically activated in HSCs. Cdx2 mice developed myelodysplastic syndrome (MDS) with progression to acute leukemia associated with stepwise acquisition of additional driver mutations. Overall design: Cdx2 DNA binding using ChIPSeq of lineage depleted bone marrow infected with retrovirus with flagged Cdx2 construct or empty vector (EV).

尾型同源盒转录因子CDX2（caudal-related homeobox transcription factor）在多数急性髓系白血病（acute myeloid leukemia, AML）患者中呈异位表达。我们构建了诱导型转基因小鼠模型，可在造血干细胞（hematopoietic stem cells, HSCs）中特异性激活Cdx2基因。该模型小鼠会罹患骨髓增生异常综合征（myelodysplastic syndrome, MDS），并随着额外驱动突变的逐步积累进展为急性白血病。整体实验设计：通过对感染携带标签CDX2构建体或空载体（empty vector, EV）的逆转录病毒的谱系耗竭骨髓进行染色质免疫沉淀测序（ChIP-seq），分析Cdx2的DNA结合特征。