Characterization of Immunoglobulin Heavy Locus Rearrangements in Molecular Subtypes of Childhood B-Cell Precursor Acute Lymphoblastic Leukemia.

Biased VDJ recombination has been previously described in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), although its causes are not yet fully understood. This study assesses differential features in 565 clonotypes from BCP-ALL molecular subsets against 560 clonotypes from bone marrow donors. Leukemia clonotypes were enriched for segments in the KMT2A rearranged and B-other subtypes, while was enriched in TCF3::PBX1. ETV6::RUNX1 presented a topological gap in the usage of central IGHV segments. BCP-ALL also presented shorter CDR3 regions, higher GC content, and lower productivity. Interestingly, productive clonotypes tended to be absent after induction therapy.