Bulletin du cancer
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Distinct clinicopathologic acute lymphoblastic leukemia (ALL) entities have been identified, resulting in the adoption of risk-oriented treatment approaches. In Philadelphia chromosome-positive (Ph(+)) ALL, the optimal treatment requires the addition of BCR-ABL tyrosine kinase inhibitors, as imatinib. However, the outcome remains poor in absence of allogeneic stem cell transplantation, and novel agents are desperately required. ⋯ Despite these therapeutic options, the cross-resistant BCR-ABL (T315I) mutation remains a major clinical challenge. The first evaluations of AP24534 present this drug as a potent multi-targeted kinase inhibitor active against T315I and all other BCR-ABL mutants. AP24534 could be the next treatment of choice in hematological malignancies with Philadelphia-positive chromosome, particularly Ph(+) ALL known for its frequent occurrence of T315I mutation.