Quy Le, Brandon Hadland, Jenny L Smith, Amanda Leonti, Benjamin J Huang, Rhonda Ries, Tiffany A Hylkema, Sommer Castro, Thao T Tang, Cyd N McKay, LaKeisha Perkins, Laura Pardo, Jay Sarthy, Amy K Beckman, Robin Williams, Rhonda Idemmili, Scott Furlan, Takashi Ishida, Lindsey Call, Shivani Srivastava, Anisha M Loeb, Filippo Milano, Suzan Imren, Shelli M Morris, Fiona Pakiam, James M Olson, Michael R Loken, Lisa Eidenschink Brodersen, Stanley R Riddell, Katherine Tarlock, Irwin D Bernstein, Keith R Loeb, Soheil Meshinchi
Fusion oncoproteins are the initiating event in the pathogenesis of many pediatric AML. The CBFA2T3-GLIS2 (C/G) fusion is a product of a cryptic translocation primarily seen in infants and early childhood and is associated with dismal outcome. Here, we demonstrate that the expression of the C/G oncogenic fusion protein promotes the transformation of human cord blood hematopoietic stem/progenitor cells (CB HSPCs) in an endothelial cell (EC) co-culture system, that recapitulates the transcriptome, morphology and immunophenotype of C/G AML and induces highly aggressive leukemia in xenograft models...
September 22, 2022: Journal of Clinical Investigation