Verena Gress, Mathieu Roussy, Luc Boulianne, Mélanie Bilodeau, Sophie Cardin, Nehme El-Hachem, Véronique Lisi, Banafsheh Khakipoor, Alexandre Rouette, Azer Farah, Louis Théret, Léo Aubert, Furat Fatima, Eric Audemard, Pierre Thibault, Éric Bonneil, Jalila Chagraoui, Louise Laramée, Patrick Gendron, Loubna Jouan, Safa Jammali, Bastien Paré, Shawn M Simpson, Thai Hoa Tran, Michel Duval, Pierre Teira, Henrique Bittencourt, Raoul Santiago, Frédéric Barabé, Guy Sauvageau, Martin A Smith, Josée Hébert, Philippe P Roux, Tanja A Gruber, Vincent-Philippe Lavallée, Brian T Wilhelm, Sonia Cellot
Acute megakaryoblastic leukemia (AMKL) is a rare, developmentally restricted and highly lethal cancer of early childhood. The paucity and hypocellularity (due to myelofibrosis) of primary patient samples hamper the discovery of cell- and genotype-specific treatments. AMKL is driven by mutually exclusive chimeric fusion oncogenes in two thirds of cases, with CBFA2T3::GLIS2 (CG2) and NUP98 fusions (NUP98r) representing the highest fatality subgroups. We established CD34+ cord blood-derived CG2 models (n=6) that sustain serial transplantation and recapitulate human leukemia regarding immunophenotype, leukemia initiating cell frequencies, co-mutational landscape and gene expression signature with distinct upregulation of the pro-survival factor BCL2...
September 20, 2023: Blood Advances