RT Journal Article
T1 Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY
A1 Mansouri, Larry
A1 Thorvaldsdottir, Birna
A1 Sutton, Lesley-Ann
A1 Karakatsoulis, Georgios
A1 Meggendorfer, Manja
A1 Parker, Helen
A1 Nadeu, Ferran
A1 Brieghel, Christian
A1 Laidou, Stamatia
A1 Moia, Riccardo
A1 Rossi, Davide
A1 Catherwood, Mark
A1 Kotaskova, Jana
A1 Delgado, Julio
A1 Rodríguez-Vicente, Ana E.
A1 Benito, Rocío
A1 Rigolin, Gian Matteo
A1 Bonfiglio, Silvia
A1 Scarfo, Lydia
A1 Mattsson, Mattias
A1 Davis, Zadie
A1 Gogia, Ajay
A1 Rani, Lata
A1 Baliakas, Panagiotis
A1 Foroughi-Asl, Hassan
A1 Jylhä, Cecilia
A1 Skaftason, Aron
A1 Rapado, Inmaculada
A1 Miras, Fátima
A1 Martínez López, Joaquín
A1 De la Serna, Javier
A1 Stamatopoulos, Kostas
A1 Rosenquist, Richard
AB 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.
PB Springer
SN 0887-6924
SN 1476-5551
YR 2022
FD 2022-12-24
LK https://hdl.handle.net/20.500.14352/111874
UL https://hdl.handle.net/20.500.14352/111874
LA eng
NO Mansouri, L., Thorvaldsdottir, B., Sutton, LA. et al. Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY. Leukemia 37, 339–347 (2023). https://doi.org/10.1038/s41375-022-01802-y
DS Docta Complutense
RD 18 abr 2025