title: Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma.
abstract: 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.
authors.affiliation: Department of Hematology-Oncology, Mayo Clinic Scottsdale, 13208 E Shea Blvd, Suite 300, Scottsdale, AZ 85259, USA.
authors.forename: Wee J
authors.initials: WJ
authors.lastname: Chng
authors.forename: Roelandt F
authors.initials: RF
authors.lastname: Schop
authors.forename: Tammy
authors.initials: T
authors.lastname: Price-Troska
authors.forename: Irene
authors.initials: I
authors.lastname: Ghobrial
authors.forename: Neil
authors.initials: N
authors.lastname: Kay
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Martha
authors.initials: M
authors.lastname: Lacy
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.forename: Philip R
authors.initials: PR
authors.lastname: Greipp
authors.forename: Renee C
authors.initials: RC
authors.lastname: Tschumper
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: Peter Leif
authors.initials: PL
authors.lastname: Bergsagel
mesh_terms: 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*
chemical_list: D015703:Antigens, CD; D015850:Interleukin-6