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Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

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Item Type:Article
Title:Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY
Creators Name:Mansouri, L. and Thorvaldsdottir, B. and Sutton, L.A. and Karakatsoulis, G. and Meggendorfer, M. and Parker, H. and Nadeu, F. and Brieghel, C. and Laidou, S. and Moia, R. and Rossi, D. and Catherwood, M. and Kotaskova, J. and Delgado, J. and Rodríguez-Vicente, A.E. and Benito, R. and Rigolin, G.M. and Bonfiglio, S. and Scarfo, L. and Mattsson, M. and Davis, Z. and Gogia, A. and Rani, L. and Baliakas, P. and Foroughi-Asl, H. and Jylhä, C. and Skaftason, A. and Rapado, I. and Miras, F. and Martinez-Lopez, J. and de la Serna, J. and Rivas, J.M.H. and Thornton, P. and Larráyoz, M.J. and Calasanz, M.J. and Fésüs, V. and Mátrai, Z. and Bödör, C. and Smedby, K.E. and Espinet, B. and Puiggros, A. and Gupta, R. and Bullinger, L. and Bosch, F. and Tazón-Vega, B. and Baran-Marszak, F. and Oscier, D. and Nguyen-Khac, F. and Zenz, T. and Terol, M.J. and Cuneo, A. and Hernández-Sánchez, M. and Pospisilova, S. and Mills, K. and Gaidano, G. and Niemann, C.U. and Campo, E. and Strefford, J.C. and Ghia, P. and Stamatopoulos, K. and Rosenquist, R.
Abstract:Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3-9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.
Keywords:Cancer Genetics, Genetics Research
Source:Leukemia
ISSN:0887-6924
Publisher:Nature Publishing Group
Date:24 December 2022
Additional Information:Erratum in: Leukemia 2023 Jan 12 (in Press)
Official Publication:https://doi.org/10.1038/s41375-022-01802-y
PubMed:View item in PubMed

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