Deletion of 9p drives B-ALL through heterozygous inactivation of Pax5 and Cd72 in preleukemic cells.
basic_science · Level V
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- Record sourced from PubMed, PMID 41701537.
- Also identified by DOI 10.1172/jci.insight.199464.
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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.
Medical subject headings
- PAX5 Transcription Factor
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
- Chromosomes, Human, Pair 9
- Chromosome Deletion
- Antigens, CD