Molecular analysis of the BCL-3 locus at chromosome 17q22 in B-cell
neoplasms
T Yano, CA Sander, RE Andrade, CE Gauwerky, CM Croce, DL Longo, ES Jaffe and M Raffeld
Hematopathology Section, National Cancer Institute, Bethesda, MD 20892.
To better understand the role of the BCL-3 locus at chromosome 17q22 in the
pathogenesis and progression of leukemias and lymphomas, we examined its
genomic configuration in 264 B-cell malignancies and its expression in a
smaller subset. Cases studied included 39 chronic lymphocytic leukemias, 58
low-grade follicular lymphomas, 20 mantle cell lymphomas, 30 small
noncleaved cell lymphomas, 25 acute lymphoblastic leukemias, 10 acquired
immunodeficiency syndrome--related non-Hodgkin's lymphomas, and 44 diffuse
mixed- or diffuse large-cell lymphomas. In addition, 38 aggressive
lymphomas (transformed follicular lymphomas) derived from previously
indolent follicular lymphomas were examined. Southern blot analysis showed
BCL-3 locus rearrangement in 4 cases (1.5%), ie, in 3 transformed
follicular lymphomas and in 1 indolent follicular lymphoma. All 4 also had
BCL-2 rearrangements consistent with their follicular center cell origin.
None of the BCL-3 rearranged cases showed MYC gene rearrangement, as
reported for the original leukemia that led to the discovery of BCL-3.
Pretransformation specimens of all three transformed follicular lymphomas
showed the presence of the BCL-3 alteration before histologic progression.
In 1 case, serial pretransformation biopsies showed that the BCL-3
rearrangement was acquired during the indolent follicular phase of the
patient's disease. Thirty lymphomas, including 2 of the 4 with BCL-3
rearrangement, were also examined for BCL-3 message. All 30, including the
2 with BCL-3 rearrangements, expressed the normal 1.7-kb BCL-3 transcript,
at approximately equivalent levels. The data indicate that, although BCL-3
locus alterations are found in only a small fraction of B-cell lymphoid
malignancies, they occur primarily in a subset of follicular center cell
lymphomas. Interestingly, these alterations appear to be acquired during
the indolent (follicular) phase of the disease and they are maintained when
histologic transformation takes place. The data also suggest that BCL-3
locus alterations do not result in gross changes of BCL-3 gene expression
and do not necessarily involve the MYC gene. Although the preferential
involvement of BCL-3 alterations in a small subset of follicular lymphomas
that transform suggests a possible link between these abnormalities and
progression, further studies are needed to ensure that these alterations
are biologically relevant and not simply a manifestation of genomic
instability.
Volume 82,
Issue 6,
pp. 1813-1819,
09/15/1993
Copyright © 1993 by The American Society of Hematology
