MLL leukemia induction by t(9;11) chromosomal translocation in human hematopoietic stem cells using genome editing.

ABSTRACT: Genome editing provides a potential approach to model de novo leukemogenesis in primary human hematopoietic stem and progenitor cells (HSPCs) through induction of chromosomal translocations by targeted DNA double-strand breaks. However, very low efficiency of translocations and lack of markers for translocated cells serve as barriers to their characterization and model development. Here, we used transcription activator-like effector nucleases to generate t(9;11) chromosomal translocations encoding MLL-AF9 and reciprocal AF9-MLL fusion products in CD34⁺ human cord blood cells. Selected cytokine combinations enabled monoclonal outgrowth and immortalization of initially rare translocated cells, which were distinguished by elevated MLL target gene expression, hi

SUBMITTER: Schneidawind C 

PROVIDER: S-EPMC5916000 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature