Immunoglobulin light chain mutational status refines IGHV prognostic value in identifying chronic lymphocytic leukemia patients with early treatment requirement.

Autor: Nabki J; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Al Deeban B; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Sium AM; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Cosentino C; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Almasri M; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Awikeh B; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Maher N; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Bellia M; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Dondolin R; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Mouhssine S; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Talotta D; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Secomandi E; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Kogila S; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Ghanej J; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Maiellaro F; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Cividini L; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Rasi S; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Chiarenza A; Division of Haematology, Ferrarotto Hospital, Catania, Italy., Olivieri J; Clinica Ematologica, Centro Trapianti e Terapie Cellulari 'Carlo Melzi' DISM, Azienda Ospedaliera Universitaria S. Maria Misericordia, Udine, Italy., Gentile M; Hematology Unit AO of Cosenza, Cosenza, Italy.; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy., Zaja F; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy., Del Principe MI; Hematology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy., Laurenti L; Dipartimento di Science di Laboratorio ed Ematologiche, Area di Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore-Roma, Rome, Italy., Bomben R; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Vit F; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Bittolo T; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Zucchetto A; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Gattei V; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Gaidano G; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy., Moia R; Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy. riccardo.moia@uniupo.it.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2024 Dec 17. Date of Electronic Publication: 2024 Dec 17.
DOI: 10.1038/s41375-024-02499-x
Abstrakt: 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). Importantly, UM light chain genes maintained an independent association with a shorter TTFT when adjusted for the IPS-E prognostic model variables, that also includes IGHV mutational status. The validation cohort of 343 Rai 0 patients confirmed these findings, with UM light chain genes predicting a 7-year treatment free probability of 42.0% versus 73.7% for M genes (p < 0.0001). These results indicate that the mutational status of the light chain genes is an independent predictor of shorter TTFT in early-stage CLL patients.
Competing Interests: Competing interests: The authors declare no competing interests. Ethics: The study was approved by local Ethical Committees (study number CE 120/19 for the training cohort; Approval n. IRB-05-2010 for the validation cohort).
(© 2024. The Author(s).)
Databáze: MEDLINE
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