Abstract
The contribution of 9p deletion to B cell acute lymphoblastic leukemia (B-ALL) has remained elusive since its discovery more than 40 years ago. Here we show that loss of CD72 is recurrent in B-ALL cases containing PAX5 deletions, and that Cd72 haploinsufficiency drives B-ALL development in Pax5+/– mice. Mechanistically, Cd72+/–;Pax5+/– precursor B cells exhibited an inflammatory transcriptional profile characterized by a decrease in Myd88 expression, a finding that aligns with our previous studies of B-ALL development in Pax5+/– mice following exposure to immune stressors. These combined genomic analyses and functional models provide compelling evidence that co-deletion of 2 contiguous genes, Pax5 and Cd72, drives B cell leukemogenesis.
Authors
Belén Ruiz-Corzo, Ana Casado-García, Ninad Oak, Paula Somoza-Cotillas, Andrea López-Álvarez de Neyra, Jorge Martínez-Cano, Alba Pérez-Pons, Elena G. Sánchez, Oscar Blanco, Diego Alonso-López, Javier De Las Rivas, Susana Riesco, Pablo Prieto-Matos, Francisco Javier García Criado, María Begoña García Cenador, Alberto Orfao, Manuel Ramírez-Orellana, César Cobaleda, Carolina Vicente-Dueñas, Kim E. Nichols, Isidro Sánchez-García
