Submitted February 22, 2006
Accepted June 5, 2006
Gene expression profiling of Waldenstrom's macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma
Wee J Chng, Roelandt 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 Leif Bergsagel*
Department of Hematology-Oncology, Mayo Clinic Scottsdale, Scottsdale, AZ, USA
Division of Hematology, Mayo Clinic College of Medicine, MN, USA
Dana Faber Cancer Institute, Boston, MA, USA
Division of Internal Medicine, Mayo Clinic College of Medicine,Mayo Graduate School Rochester,MN,USA
Department of Immunology and Division of Hematology, Mayo Clinic College of Medicine, MN, USA
* Corresponding author; email: bergsagel.leif{at}mayo.edu.
Waldenstrom's 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 pathological 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.
