Clinical Management of Philadelphia Chromosome-Positive and ABL-Class Fusion-Positive Acute Lymphoblastic Leukemia

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is characterized by the constitutively activated BCR::ABL1 gene fusion and was historically associated with a dismal outcome. Next-generation sequencing studies have identified an increasing number of ABL-class fusions other than BCR::ABL1 among ALL patients who exhibit a similar gene expression profile compared to that of Ph+ ALL patients; hence, these patients are referred to as ABL-class Ph-like ALL or ABL-class fusion-positive ALL. Patients with Ph+ ALL and ABL-class fusion-positive ALL often present with adverse clinical features, poor response to conventional chemotherapy, higher rates of relapse and harbor kinase fusions that are amenable to treatment with ABL-directed tyrosine kinase inhibitors. The successful combination of imatinib and intensive chemotherapy has established a new treatment paradigm for pediatric Ph+ ALL that could potentially benefit ABL-class Ph-like ALL, thus expanding the horizons of precision medicine in ALL. We herein review the clinical characteristics, genomic features, and treatment opportunities for Ph+ ALL and ABL-class fusion-positive ALL.