Molecular determinants of clinical outcomes in a real-world diffuse large B-cell lymphoma population.

Autor: Alduaij W; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; UBC Clinician Investigator Program, The University of British Columbia, Vancouver, BC, Canada., Collinge B; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada., Ben-Neriah S; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Jiang A; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada., Hilton LK; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Boyle M; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Meissner B; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Chong L; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Miyata-Takata T; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Slack GW; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada., Farinha P; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada., Craig JW; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada., Lytle A; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada., Savage KJ; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada., Villa D; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada., Gerrie AS; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada., Freeman CL; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada., Gascoyne RD; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Connors JM; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Morin RD; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada., Sehn LH; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada., Mungall AJ; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada., Steidl C; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada., Scott DW; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada.
Jazyk: angličtina
Zdroj: Blood [Blood] 2023 May 18; Vol. 141 (20), pp. 2493-2507.
DOI: 10.1182/blood.2022018248
Abstrakt: Molecular heterogeneity of diffuse large B-cell lymphoma (DLBCL) underlies the variable outcomes achieved with immunochemotherapy. However, outcomes of gene expression profiling (GEP)-defined molecular subgroups in a real-world DLBCL population remain unknown. Here we examined the prevalence and outcomes of molecular subgroups in an unselected population of 1149 patients with de novo DLBCL in British Columbia, Canada. Evaluable biopsies were profiled by fluorescence in situ hybridization (FISH), immunohistochemistry, and digital GEP to assign cell-of-origin and the so-called "double-hit signature" (DHITsig)-a signature originally described as being characteristic for high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2). DHITsig was expressed in 21% of 431 germinal center B-cell-like (GCB)-DLBCL and all 55 Burkitt lymphomas examined. Reflecting this latter finding, DHITsig has been renamed the "dark zone signature" (DZsig). DZsigpos-DLBCL, non-DZsigpos GCB-DLBCL and activated B-cell-like (ABC)-DLBCL were associated with a 2 year overall survival of 57%, 89%, and 71%, respectively. 62% of DZsigpos tumors were negative for HGBCL-DH-BCL2 by FISH, but were associated with outcomes similar to HGBCL-DH-BCL2. A small group of HGBCL-DH-BCL2 that lacked DZsig expression had different molecular features compared with DZsig-expressing HGBCL-DH-BCL2 and were associated with favorable outcomes comparable to DLBCL, not otherwise specified. DZsigpos and ABC-DLBCL had a shorter diagnosis-to-treatment interval (DTI) than GCB-DLBCL, with this metric being associated with outcome. In conclusion, DZsig expression extends beyond HGBCL-DH-BCL2 and captures a poor-prognosis DLBCL subgroup with short DTI, including patients unidentifiable by routine FISH testing, that should be considered for treatment intensification or novel therapies in prospective trials.
(© 2023 by The American Society of Hematology.)
Databáze: MEDLINE