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Deletion of 9p drives B-ALL through heterozygous inactivation of Pax5 and Cd72 in preleukemic cells

2026/02/17 by Belén Ruiz-Corzo, Ana Casado-García, Ninad Oak +18 · 1 voice
Medicine · #Acute Lymphoblastic Leukemia research #Acute Myeloid Leukemia Research #Chronic Myeloid Leukemia Treatments

paper · pdf · doi:10.1172/jci.insight.199464

openalex publication_date 2026/02/17 · openalex created_date 2026/02/18 · openalex updated_date 2026/08/01

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.

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