Acute lymphoblastic leukemia (ALL) is classified into various genomic subtypes. BCR-ABL1-like, or Philadelphia chromosome-like ALL (Ph-like ALL), is characterized by a gene expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and poor outcomes. However, the frequency and spectrum of genetic alterations in Ph-ALL and their responsiveness to tyrosine kinase inhibitors are unknown. In this genomic profiling study, we identified the frequency of Ph-like ALL in children and in young adults with ALL, spectrum of kinase-activating alterations in Ph-like ALL, and the alterations sensitive to tyrosine kinase and/or JAK pathway inhibitors. Findings from this study have guided the design of precision medicine therapy in the TOT-17 protocol, a major frontline treatment for childhood ALL at St Jude Children’s Research Hospital.
Roberts K … Cheng C … Mullighan C et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. New England Journal of Medicine, 371:1005-1015, 2014. PMCID: PMC4191900.