Modeling leukemia with pediatric acute leukemia patient-derived iPSCs

2021 
Abstract Objective ediatric acute leukemia (AL) is the most common hematological malignancy in childhood. However, the limitation of clinical specimens hindered the progress of research. Therefore, new research platforms are urgently needed to establish and clarify the pathogenesis of pediatric AL, and it is necessary to try to find novel targeted therapies for the clinical use. Here, the induced pluripotent stem cells (iPSCs) derived from AL provide a reliable model for basic research. Methods eukemia cells were sorted by flow cytometry and then reprogrammed into iPSCs by Sendai virus. Cell cycle assay was used to analyze cell proliferation. Results iPS cell lines from T cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) cells were successfully established. The reprogramming efficiency of AML cells was much higher than that of ALL cells. Disease iPS cells switched off the expression of the disease marker genes at iPS and HPC stage. When different subtypes of AML-iPSCs were differentiated into hematopoietic progenitor cells, iPS derived from acute megakaryocytic leukemia was more readily differentiated into megakaryocyte-erythroid progenitors. Whereas, the differentiation of multipotent lymphoid progenitor (MLP) and granulocyte macrophage progenitor (GMP) were blocked. The iPS derived from acute monocyte leukemia (AMCL) also showed the differentiation of common myeloid progenitors (CMP), GMP and monocytes significantly increased but MLP differentiation was inhibited. The AML-iPSC could form teratomas and we could obverse three germ layers in vivo, indicating that the AML-iPSCs have full pluripotency. However, there were not enough blood cells in teratoma to identify the leukemia. Conclusions Our results provide a novel platform for AL research and critical insight into the difference of hematopoietic differentiation between ALL and AML.
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