Functional consequence and therapeutic targeting of cryptic ALK fusions in monosomy 7 acute myeloid leukemia

Acute myeloid leukemia (AML) patients have a wide array of cytogenetic and molecular aberrations, which can influence response to therapy. Monosomy 7 is a rare subset within pediatric AML (prevalence of <2%) that is highly associated with poor outcomes. Fusions involving the anaplastic tyrosine kinase (ALK) gene were exclusively identified in 14.3% of this high-risk cohort, while absent across all other AML. Given the dismal outcomes of monosomy 7, 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.

Automated summary

Patients with acute myeloid leukemia (AML) can have different genetic and molecular abnormalities that affect their response to treatment. Monosomy 7 is a rare subset of pediatric AML (prevalence of <2%) that is associated with poor outcomes. Fusions involving the anaplastic tyrosine kinase (ALK) gene were found exclusively in 14.3% of high-risk monosomy 7 cases, but not in other forms of AML. The use of the FDA-approved tyrosine kinase inhibitor, crizotinib, may be a promising therapy for these patients.