biostudies-literatureUnknown39(3)Nabki JThe mutational status of immunoglobulin (IG) light chain genes in chronic lymphocytic leukemia (CLL) and its clinical impact have not been extensively studied. To assess their prognostic significance, the IG light chain gene repertoire in CLL patients has been evaluated using a training-validation approach. In the training cohort (N = 573 CLL), 92.5% showed productive IG light chain genes rearrangements, with IGKV4-1 (20.5%) and IGLV3-21 (19.0%) being the most common. A 99.0% somatic hypermutation cut-off was identified as the best predictor for time to first treatment (TTFT) in 414 Binet A CLL patients of the training cohort. Patients with unmutated (UM) light chain genes displayed a 10-year treatment free probability of 32.4% versus 73.2% for those with mutated (M) genes (p < 0.0001). ImLeukemia643-649https://www.ebi.ac.uk/biostudies/studies/S-EPMC11879880biostudies-literatureImmunoglobulin light chain mutational status refines IGHV prognostic value in identifying chronic lymphocytic leukemia patients with early treatment requirement.PMC11879880Ghanej JKogila SCividini LSium AMMaiellaro FVit FCosentino CBittolo TAwikeh BOlivieri JChiarenza ATalotta DMaher NGentile MGattei VRasi SSecomandi EZucchetto ABomben RAl Deeban BAlmasri MNabki JDel Principe MILaurenti LZaja FBellia MMouhssine SDondolin RGaidano GMoia RfalseImmunoglobulin light chain mutational status refines IGHV prognostic value in identifying chronic lymphocytic leukemia patients with early treatment requirement.The mutational status of immunoglobulin (IG) light chain genes in chronic lymphocytic leukemia (CLL) and its clinical impact have not been extensively studied. To assess their prognostic significance, the IG light chain gene repertoire in CLL patients has been evaluated using a training-validation approach. In the training cohort (N = 573 CLL), 92.5% showed productive IG light chain genes rearrangements, with IGKV4-1 (20.5%) and IGLV3-21 (19.0%) being the most common. A 99.0% somatic hypermutation cut-off was identified as the best predictor for time to first treatment (TTFT) in 414 Binet A CLL patients of the training cohort. Patients with unmutated (UM) light chain genes displayed a 10-year treatment free probability of 32.4% versus 73.2% for those with mutated (M) genes (p < 0.0001). Im2025-01-01T00:00:00Z2025 Mar2025-04-19T17:34:23.936Z2025-04-19T17:34:23.936ZS-EPMC118798803969018210.1038/s41375-024-02499-x