CRISPR-Cas9-induced t(11;19)/MLL-ENL translocations initiate leukemia in human hematopoietic progenitor cells in vivo.

ABSTRACT: Chromosomal translocations that generate oncogenic fusion proteins are causative for most pediatric leukemias and frequently affect the MLL/KMT2A gene. In vivo modeling of bona fide chromosomal translocations in human hematopoietic stem and progenitor cells is challenging but essential to determine their actual leukemogenic potential. We therefore developed an advanced lentiviral CRISPR-Cas9 vector that efficiently transduced human CD34⁺ hematopoietic stem and progenitor cells and induced the t(11;19)/MLL-ENL translocation. Leveraging this system, we could demonstrate that hematopoietic stem and progenitor cells harboring the translocation showed only a transient clonal growth advantage in vitro In contrast, t(11;19)/MLL-ENL-harboring CD34⁺

SUBMITTER: Reimer J 

PROVIDER: S-EPMC5685230 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature