Sequence and expression analyses of μ and δ transcripts in patients with waldenström's macroglobulinemia

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Abstract
Waldenström's macroglobulinemia (WM) is a malignant lymphoplasmo‐proliferative disorder with monoclonal pentameric immunoglobulin (Ig)M production. The most consistent feature of clonal B cells in the bone marrow (BM) and/or lymph nodes of patients with WM is the presence of pleomorphic B‐lineage cells at different stages of maturation, such as small lymphocytes, lymphoplasmacytoid cells, and plasma cells. Monoclonal lymphocytes express μ chains with or without δ chains. A recent DNA analysis of WM tumor clones showed WM to be derived from B cells that have been selected by antigen at a relatively late stage of differentiation. To further clarify the origin of WM tumor cells, we analyzed the variable (V) domain sequences of tumor derived μ and δ transcripts. The expression of δ transcripts was also examined in peripheral blood (PB) and BM using the reverse transcriptase polymerase chain reaction (RT‐PCR) combined with a single‐strand conformation polymorphism (SSCP) analysis. The sequences were identical among the μ and δ transcripts in each patient and the level of somatic mutation in the VH regions expressed by tumor cells was in the same range as that of IgM‐only B cells and IgM+IgD+ memory B cells. In our previous RT‐PCR‐SSCP analysis, a single dominant band of the μ isotype was observed in BM and PB in all patients. However, common dominant bands in BM and PB were detected in only one patient in a δ transcript analysis. In the rest of the patients, monoclonal δ transcripts were only detected in BM. Our results suggest that a normal counterpart of WM cells is somatically mutated IgM+IgD+ and/or IgM‐only B cells and the expression patterns of monoclonal μ and δ transcripts differ between BM and PB in some cases of WM. Am. J. Hematol. 68:139–143, 2001.

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