Clinical screening for Ph-like ALL and the developing role of TKIs

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a common subtype of B-lineage acute lymphoblastic leukemia (B-ALL) with increasing frequency across the age spectrum. Characterized by a kinase-activated gene expression profile and driven by a variety of genetic alterations involving cytokine receptors and kinases, Ph-like ALL is associated with high rates of residual disease and relapse in patients treated with conventional chemotherapy. In this case-based review, we describe the biology of the 2 major ABL-class and JAK pathway genetic subtypes of Ph-like ALL, discuss current diagnostic testing methodologies, and highlight targeted inhibitor and chemo/immunotherapy approaches under clinical investigation in children, adolescents, and adults with these high-risk leukemias.