Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblastic leukemia

Abstract B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by genetic alterations with high heterogeneity. Precise subtypes distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology. Most of these profiles are associated recurrent non-overlapping rearrangements or hotspot point mutations that analogous to the established subtypes, such as DUX4 rearrangements, MEF2D ZNF384/ZNF362 NUTM1 BCL2/MYC BCL6 ETV6-RUNX1 -like expression, PAX5alt (diverse PAX5 alterations, including intragenic amplifications, mutations), and (p.Pro80Arg) biallelic IKZF1 (p.Asn159Tyr), ZEB2 (p.His1038Arg). These molecular could be classified RNA-seq Refined classification greatly improved treatment strategy. Multiagent therapy regimens, target inhibitors (e.g., imatinib), immunomodulators, monoclonal antibodies, chimeric antigen receptor T-cell (CAR-T) therapy, transforming clinical practice from chemotherapy drugs personalized medicine in field risk-directed disease management. We provide an update on our knowledge emerging therapeutic targets BCP-ALL.