Nup98-Kdm5a, induced via CRISPR-Cas9 genome editing, transforms murine hematopoietic stem cells

Introduction: Pediatric acute megakaryoblastic leukemia is characterized by unique recurrent chromosomal translocations (CTs) with NUP98-KDM 5A being one of the most frequent. However, adequat models to investigate the role of NUP98-KDM 5A in non-DS-AMKL are yet to be established. Methods: A lentiviral CRISPR-Cas9 vector containing two sgRNAs to generate the Nup98-Kdm5a translocation was generated and introduced into murine lineage-, Sca1+, cKit+ (LSK) cells to evaluate the effects of endogenous Nup98-Kdm5a in vitro and in vivo. Results: Expression of the Nup98-Kdm5a fusion gene was detectable in transduced muri…