Genomic Basis of B-Cell Precursor Acute Lymphoblastic Leukemia

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) represents a malignancy originating from B-lineage lymphoid progenitor cells. It encompasses various distinct subtypes, each characterized by distinct patterns of genetic changes such as aneuploidy, chromosomal reconfigurations, DNA copy number variations, and sequence mutations [1–4]. The emergence of next-generation sequencing technology has revolutionized genomic analysis, enabling a comprehensive understanding of the genomic anomalies within BCP-ALL cases among children, adolescents, and young adults (AYAs) [5, 6]. Accurately identifying the genetic abnormalities driving BCP-ALL holds significance not only for risk stratification but also for integrating molecularly targeted therapeutic strategies [7, 8]. The subtypes of BCP-ALL are currently categorized into four groups based on the underlying driver alterations: (1) chromosomal abnormalities (aneuploidy, iAMP21), (2) fusion oncoproteins driven by transcription factors (TFs) or oncogenes (ETV6::RUNX1, TCF3::PBX1, KMT2A-, HLF-, ZNF384-, NUTM1-, MEF2D-rearranged), rearrangements/translocations (DUX4-, MYC-rearranged, CDX2/UBTF), as well as point mutations (PAX5 P80R, IKZF1 N159Y), (3) kinase-driven alterations (BCR::ABL1, BCR::ABL1-like), and (4) other provisional entities (phenocopies of certain known subtypes, PAX5-altered (PAX5alt), ZEB2/IGH::CEBPE). In this section, we review the current genetic classification of BCP-ALL.