Molecular subtypes and genetic diagnostics in B-cell acute lymphoblastic leukemia

The molecular classification of B-cell acute lymphoblastic leukemia (B-ALL) has evolved substantially with the introduction of genome-wide technologies for diagnosis, leading to the recognition of numerous genetic subtypes with distinct biological and prognostic implications. While historically defined chromosomal subgroups remain central to current classification systems, genomic profiling has enabled the identification of additional entities that were previously designated as not otherwise specified (NOS) in older classification schemes. Accurate recognition of these ALL subtypes is important for risk stratification, prognostic assessment, and the expanding use of targeted therapies. However, implementation of comprehensive genomic testing remains challenging because multiple complementary diagnostic techniques are often required for complete assessment and advanced sequencing approaches are not universally available. This review briefly summarizes the morphologic and immunophenotypic features of B-ALL and then focuses on the current molecular classification of B-ALL, highlighting the genetic features of established and newly recognized subtypes, their clinical significance, and the diagnostic approaches used for their identification. Future efforts should focus on integrating genomic classification, secondary genetic alterations, and measurable residual disease (MRD) assessment to further refine risk-adapted and personalized treatment strategies.