TY - JOUR
T1 - Cell of origin of transformed follicular lymphoma
AU - Kridel, Robert
AU - Mottok, Anja
AU - Farinha, Pedro
AU - Ben-Neriah, Susana
AU - Ennishi, Daisuke
AU - Zheng, Yvonne
AU - Chavez, Elizabeth A.
AU - Shulha, Hennady P.
AU - Tan, King
AU - Chan, Fong Chun
AU - Boyle, Merrill
AU - Meissner, Barbara
AU - Telenius, Adele
AU - Sehn, Laurie H.
AU - Marra, Marco A.
AU - Shah, Sohrab P.
AU - Steidl, Christian
AU - Connors, Joseph M.
AU - Scott, David W.
AU - Gascoyne, Randy D.
N1 - Publisher Copyright:
© 2015 by The American Society of Hematology.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2015/10/29
Y1 - 2015/10/29
N2 - Follicular lymphoma (FL) is an indolent disease but transformsin2%to3%of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporalchangesof routinely availablebiomarkers,outcome after transformation, as well as molecular subtypesofTFL.We report that the expressionof IRF4 is anindependent predictor of early transformation (Hazard ratio, 13.3; P < .001).We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell-like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL.
AB - Follicular lymphoma (FL) is an indolent disease but transformsin2%to3%of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporalchangesof routinely availablebiomarkers,outcome after transformation, as well as molecular subtypesofTFL.We report that the expressionof IRF4 is anindependent predictor of early transformation (Hazard ratio, 13.3; P < .001).We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell-like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL.
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U2 - 10.1182/blood-2015-06-649905
DO - 10.1182/blood-2015-06-649905
M3 - Article
C2 - 26307535
AN - SCOPUS:84945925972
VL - 126
SP - 2118
EP - 2127
JO - Blood
JF - Blood
SN - 0006-4971
IS - 18
ER -