Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma.
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.
Chng
Wee J
WJ
Department of Hematology-Oncology, Mayo Clinic Scottsdale, 13208 E Shea Blvd, Suite 300, Scottsdale, AZ 85259, USA.
Schop
Roelandt F
RF
Price-Troska
Tammy
T
Ghobrial
Irene
I
Kay
Neil
N
Jelinek
Diane F
DF
Gertz
Morie A
MA
Dispenzieri
Angela
A
Lacy
Martha
M
Kyle
Robert A
RA
Greipp
Philip R
PR
Tschumper
Renee C
RC
Fonseca
Rafael
R
Bergsagel
Peter Leif
PL
D015703:Antigens, CD / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000235:genetics; D009101:Multiple Myeloma / Q000235:genetics*; D010641:Phenotype; D010950:Plasma Cells / Q000378:metabolism; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics*
D015703:Antigens, CD; D015850:Interleukin-6