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Blood, 15 October 2002, Vol. 100, No. 8, pp. 2996-3001
NEOPLASIA
Waldenström macroglobulinemia neoplastic cells lack
immunoglobulin heavy chain locus translocations but have frequent
6q deletions
Roelandt F. J. Schop,
W.
Michael Kuehl,
Scott A. Van
Wier,
Gregory J. Ahmann,
Tammy Price-Troska,
Richard J. Bailey,
Syed M. Jalal,
Ying Qi,
Robert A. Kyle,
Philip R. Greipp, and
Rafael Fonseca
From the Department of Hematology and Internal Medicine
and the Department of Laboratory Medicine and Pathology, Mayo Clinic,
Rochester, MN; and the National Cancer Institute, Genetics Branch,
Bethesda MD.
Lymphoplasmacytic lymphoma (LPL) is characterized by
t(9;14)(p13;q32) in 50% of patients who lack paraproteinemia.
Waldenström macroglobulinemia (WM), which has an immunoglobulin M
(IgM) paraproteinemia, is classified as an LPL. Rare reports have
suggested that WM sometimes is associated with 14q23 translocations,
deletions of 6q, and t(11;18)(q21;q21). We tested for these
abnormalities in the clonal cells of WM patients. We selected patients
with clinicopathologic diagnosis of WM (all had IgM levels greater than
1.5 g/dL). Southern blot assay was used to detect legitimate and
illegitimate IgH switch rearrangements. In addition to conventional
cytogenetic (CC) and multicolor metaphase fluorescence in situ
hybridization (M-FISH) analyses, we used interphase FISH to screen for
t(9;14)(p13;q32) and other IgH translocations, t(11;18)(q21;q21),
and 6q21 deletions. Genomic stability was also assessed using
chromosome enumeration probes for chromosomes 7, 9, 11, 12, 15, and 17 in 15 patients. There was no evidence of either legitimate or
illegitimate IgH rearrangements by Southern blot assay (n = 12). CC
(n = 37), M-FISH (n = 5), and interphase FISH (n = 42) failed to
identify IgH or t(11;18) translocations. Although tumor cells from most
patients were diploid for the chromosomes studied, deletions of 6q21
were observed in 42% of patients. In contrast to LPL tumors that are not associated with paraproteinemia and that have frequent
t(9;14)(p13;q32) translocations, IgH translocations are not found in
WM, a form of LPL tumor distinguished by IgM paraproteinemia. However,
WM tumor cells, which appear to be diploid or near diploid, often have
deletions of 6q21.
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