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Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 3081-3087
Correlation of Bcl-2 Rearrangement With Clinical
Characteristics and Outcome in Indolent Follicular Lymphoma
Armando López-Guillermo,
Fernando Cabanillas,
Timothy I. McDonnell,
Peter McLaughlin,
Terry Smith,
William Pugh,
Fredrick Hagemeister,
M. Alma Rodríguez,
Jorge E. Romaguera,
Anas Younes,
Andreas H. Sarris,
H. Alejandro Preti, and
Ming-Seng Lee
From the Departments of Myeloma/Lymphoma, Pathology, Biomathematics,
and Laboratory Medicine, the University of Texas, M.D. Anderson Cancer
Center, Houston, TX.
The t(14;18) translocation, which involves the bcl-2
oncogene, occurs in follicular lymphomas (FL) at two common sites: the major breakpoint region (MBR) and the minor cluster region
(mcr). The biological and clinical significance of these
breakpoints is unknown. The bcl-2 breakpoint site was
determined in 247 previously untreated patients (49% men; median age
52 years) with indolent FL (155 grade I, 83 grade II, and 8 grade III)
to correlate it with pretreatment characteristics, response, and
outcome. The bcl-2 breakpoint site was determined by a
polymerase chain reaction method of peripheral blood (all cases), bone
marrows (149 cases), and fresh lymph node biopsy specimens (68 cases).
The breakpoint site occurred at MBR in 175 cases (71%) and at
mcr in 27 (11%). In 45 cases (18%), no breakpoint was
detected (germline). No significant relationship was found between the
rearrangements and the expression of BLC-2 and BAX
proteins. Patients' germline for MBR and mcr tended to
present more frequently with stage IV disease and higher  2-microglobulin (2M) levels, whereas mcr-rearranged
patients presented more frequently with early stage and normal 2M.
The complete response rate of germline patients was significantly lower
than that of MBR and mcr patients. An estimated 3-year
failure-free survival (FFS) for mcr, MBR, and germline cases
was 95%, 76%, and 57%, respectively (P < .001). The
bcl-2 breakpoint site was independent of serum 2M and
lactate dehydrogenase in its correlation with FFS. In conclusion, the
bcl-2 rearrangement site is an important prognostic factor in
indolent FL, useful to identify patients who may require different treatment.
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