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This study assesses differential features in 565 <jats:italic>IGH<\/jats:italic> clonotypes from BCP\u2010ALL molecular subsets against 560 clonotypes from bone marrow donors. Leukemia clonotypes were enriched for <jats:italic>IGHV6\u20101<\/jats:italic> segments in the KMT2A rearranged and B\u2010other subtypes, while <jats:italic>IGHV3\u201023<\/jats:italic> was enriched in TCF3::PBX1. ETV6::RUNX1 presented a topological gap in the usage of central IGHV segments. BCP\u2010ALL also presented shorter CDR3 regions, higher GC content, and lower productivity. 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