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Blood, 15 May 2002, Vol. 99, No. 10, pp. 3735-3741
NEOPLASIA
Myeloma and the t(11;14)(q13;q32); evidence for a biologically
defined unique subset of patients
Rafael Fonseca,
Emily A. Blood,
Martin M. Oken,
Robert A. Kyle,
Gordon W. Dewald,
Richard J. Bailey,
Scott A. Van
Wier,
Kimberly J. Henderson,
James D. Hoyer,
David Harrington,
Neil E. Kay,
Brian Van Ness, and
Philip R. Greipp
From the Mayo Clinic Department of Hematology and
Internal Medicine, Department of Pathology and Laboratory Medicine, and
ECOG Statistical Center, Dana Farber Cancer Institute, Boston,
MA; Virginia Piper Cancer Institute, Minneapolis, MN; and
University of Minnesota, Minneapolis, MN.
The t(11;14)(q13;q32) results in up-regulation of cyclin
D1 and is the most common translocation detected in multiple
myeloma, where it is also associated with a lymphoplasmacytic
morphology. We performed an interphase fluorescent in situ
hybridization (FISH) study to determine the clinical and biologic
significance of the abnormality when testing a large cohort of myeloma
patients. Bone marrow slides from multiple myeloma patients entered
into the Eastern Cooperative Oncology Group phase III clinical trial
E9486 and associated laboratory correlative study E9487 were analyzed using interphase FISH combined with immune-fluorescent (cytoplasmic immunoglobulin-FISH) detection of clonal plasma cells. We used FISH
probes that hybridize to the 14q32 and 11q13 chromosomal loci. The
t(11;14)(q13;q32) was correlated with known biologic and prognostic
factors. Of 336 evaluable patients, 53 (16%) had abnormal FISH
patterns compatible with the t(11;14)(q13;q32). These patients appeared
to be more likely to have a serum monoclonal protein of less than 10 g/L (1 g/dL) (28% vs 15%, P = .029) and a lower plasma
cell labeling index (P = .09). More strikingly, patients
were less likely to be hyperdiploid by DNA content analysis (n = 251,
14% vs 62%, P < .001). Patients with the t(11;14)(q13;q32) appeared to have better survival and response to treatment, although this did not reach statistical significance. Multiple myeloma with the
t(11;14)(q13;q32) is a unique subset of patients, not only
characterized by cyclin D1 up-regulation and a
lymphoplasmacytic morphology, but is also more frequently associated
with small serum monoclonal proteins and is much less likely to be
hyperdiploid. These patients do not have a worsened prognosis as
previously thought.
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