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Blood, 1 February 2003, Vol. 101, No. 3, pp. 1149-1154
NEOPLASIA
Follicular lymphoma grade 3B includes 3 cytogenetically
defined subgroups with primary t(14;18), 3q27, or other
translocations: t(14;18) and 3q27 are mutually exclusive
Anneke G. Bosga-Bouwer,
Gustaaf W. van Imhoff,
Ronald Boonstra,
Anneke van der
Veen,
Eugenia Haralambieva,
Anke van den Berg,
Bauke de Jong,
Vanessa Krause,
Martin C. Palmer,
Robert Coupland,
Philip M. Kluin,
Eva van den Berg, and
Sibrand Poppema
From the Departments of Genetics, Hematology, and
Pathology & Laboratory Medicine, University Medical Center Groningen,
The Netherlands; and Cross Cancer Institute, Edmonton, AB,
Canada.
Chromosomal translocations involving t(14;18)(q32;q21) and the
chromosome 3q27 region are common in B-cell non-Hodgkin lymphoma of
germinal center cell origin. Grade 3B follicular lymphoma (FL), consisting almost exclusively of centroblasts, is a distinct subgroup of follicular lymphomas that has more in common clinically with the
aggressive diffuse large B-cell lymphomas than with their indolent FL
grade 1 and 2 counterparts. We studied the cytogenetic and molecular
genetic aberrations by classic cytogenetics, polymerase chain reaction,
Southern blot hybridization, and fluorescence in situ hybridization,
with special emphasis on t(14;18), affecting bcl-2, and
3q27 rearrangement, affecting bcl-6, in 32 cases of FL
grade 3B. Three distinctive subgroups were identified based upon the
existence of breakpoint 3q27, a translocation t(14;18), or the absence
of both. Group I involved a t(14;18) and no 3q27 aberrations
(n = 13); group II was without a t(14;18) and without 3q27
aberrations (n = 9), but had other cytogenetic aberrations; and group
III was without a t(14;18) but with aberrations involving 3q27
(n = 10). None of the FL grade 3B cases harbored both a t(14;18) and
3q27 aberration. These results, in particular the finding of a mutual
exclusiveness of bcl-2 and bcl-6 rearrangement,
indicate at least 3 different pathways of oncogenesis in FL grade 3B.
FL grade 3B with bcl-2 rearrangement probably is part of
the same entity as the other follicular lymphomas (1, 2, 3A), whereas
the cases with 3q27 abnormalities or other unrelated translocations are
more closely related to the majority of diffuse large-cell lymphomas of
germinal center cell origin.
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