Functional Consequence and Therapeutic Targeting of Cryptic ALK Fusions (ALK fus ) in Monosomy7 AML

Acute Myeloid Leukemia (AML) patients have a wide array of cytogenetic and molecular aberrations which can influence response to therapy. Monosomy7 (Mono7) is a rare subset within pediatric AML (prevalence of 4-5%), that is highly associated with poor outcomes. Fusions involving the ALK gene (14.3%) were exclusively identified within this high-risk cohort while absent across all other AML. Given the dismal outcomes of Mono7, we evaluated the use of crizotinib, an FDA-approved tyrosine kinase inhibitor, used to treat patients with ALK fusions. Our findings suggest that crizotinib may serve as a novel therapy for these patients.