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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2755-2763.
Prepublished online as a Blood First Edition Paper on June 27, 2006; DOI 10.1182/blood-2006-02-005488.
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NEOPLASIA
Gene-expression profiling of Waldenström macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma
Wee J. Chng,
Roelandt F. Schop,
Tammy Price-Troska,
Irene Ghobrial,
Neil Kay,
Diane F. Jelinek,
Morie A. Gertz,
Angela Dispenzieri,
Martha Lacy,
Robert A. Kyle,
Philip R. Greipp,
Renee C. Tschumper,
Rafael Fonseca, and
Peter Leif Bergsagel
From the Department of Hematology-Oncology, Mayo Clinic Scottsdale, AZ; Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN; Dana Faber Cancer Institute, Boston, MA; Division of Internal Medicine, Mayo Clinic College of Medicine, Mayo Graduate School, Rochester, MN; Department of Immunology and Division of Hematology, Mayo Clinic College of Medicine, Mayo Graduate School, Rochester, MN.
Waldenström macroglobulinemia (WM) is a B-cell malignancy characterized by the ability of the B-cell clone to differentiate into plasma cells. Although the clinical syndrome and the pathologic characteristics are well defined, little is known about its biology and controversy still exists regarding its cell of origin. In this gene-expression study, we compared the transcription profiles of WM with those of other malignant B cells including (chronic lymphocytic leukemia [CLL] and multiple myeloma [MM]) as well as normal cells (peripheral-blood B cells and bone marrow plasma cells). We found that WM has a homogenous gene expression regardless of 6q deletion status and clusters with CLL and normal B cells on unsupervised clustering with very similar expression profiles. Only a small gene set has expression profiles unique to WM compared to CLL and MM. The most significantly up-regulated gene is IL6 and the most significantly associated pathway for this set of genes is MAPK signaling. Thus, IL6 and its downstream signaling may be of biologic importance in WM. Further elucidation of the role of IL-6 in WM is warranted as this may offer a potential therapeutic avenue.

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