Future prospects in the diagnosis and treatment of Philadelphia chromosome-like acute lymphoblastic leukemia

Abstract

 Philadelphia chromosome-like (also known as BCR-ABL1-like) acute lymphoblastic leukemia (Ph-like ALL) is a new high-risk subtype of B-cell ALL (B-ALL) that exhibits a mRNA expression profile similar to that of Ph positive ALL. Ph-like ALL patients harbor a variety of gene alterations that activate kinase and cytokine receptor signaling pathways. Ph-like ALL are subcategorized into the following three groups based on gene alterations: 1) JAK/STAT type; 2) ABL-class type and 3) others. Preclinical studies and case reports in human show efficacy of kinase inhibitors targeting activated signaling pathways, such as JAK inhibitor and tyrosine kinase inhibitor. Several clinical trials to assess the efficacy of Ruxolitinib and Dasatinib are in progress for JAK/STAT- and ABL-class- type Ph-like ALL patients, respectively; however, their diagnostic methods and therapeutic strategies are not fully generalized. Development of new diagnostic and therapeutic strategies are in need to improve their clinical outcomes.