Failure of CDKN2A/B (INK4A/B–ARF)-mediated tumor suppression and resistance to targeted therapy in acute lymphoblastic leukemia induced by BCR-ABL

Abstract

Deletions of the CDKN2A/B tumor suppressor locus and of the IKAROS and PAX5 genes that promote B-lineage development occur frequently in lymphoid, but not myeloid leukemias initiated by the BCR-ABL tyrosine kinase. Why is this the case, and how do these genetic lesions contribute to an aggressive disease that fails to durably respond to targeted kinase inhibitors?