title: Expression of regulatory genes for lymphoplasmacytic cell differentiation in Waldenstrom Macroglobulinemia.
abstract: Waldenstrom Macroglobulinemia (WM) is a B-cell malignancy characterized by excess bone marrow (BM) lymphoplasmacytic cells (LPC). The accumulation of LPC in WM may represent a failure of B-cells to properly differentiate into plasma cells. The present study investigated transcriptional expression of genes involved in late B-cell differentiation, including PRDM1, PAX5, XBP1 transcripts and ERN1, in BM B-cells from 31 patients with WM and six healthy donors. Real time reverse transcription polymerase chain reaction (RT-PCR) determined that approximately 80% of the patients had high XBP1 spliced mRNA expression, 80% of whom had high mRNA ERN1alpha expression. XBP1, PRDM1 and PAX5 mRNA was present in all patients studied. Using relative quantitative RT-PCR we isolated two groups with low and high expression of XBP1, XBP1 spliced and ERN1alpha. Sequence analysis showed germline polymorphisms in all genes studied. These data depict for the first time a heterogeneous expression pattern of the genes involved in late differentiation process of plasma cells in patients with WM and propose a role of XBP1-ERN1alpha in WM pathogenesis.
authors.affiliation: Bing Center for Waldenstrom's Macroglobulinemia and Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Hunter
authors.forename: Lian
authors.initials: L
authors.lastname: Xu
authors.forename: Aldo M
authors.initials: AM
authors.lastname: Roccaro
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Moreau
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Santos
authors.forename: Evdoxia
authors.initials: E
authors.lastname: Hatjiharissi
authors.forename: Vinod
authors.initials: V
authors.lastname: Bakthavachalam
authors.forename: Sophia
authors.initials: S
authors.lastname: Adamia
authors.forename: Allen W
authors.initials: AW
authors.lastname: Ho
authors.forename: Jacob
authors.initials: J
authors.lastname: Soumerai
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Patterson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Manning
authors.forename: Susanna
authors.initials: S
authors.lastname: Hamilton
authors.forename: Sigitas
authors.initials: S
authors.lastname: Verselis
authors.forename: Edward
authors.initials: E
authors.lastname: Fox
authors.forename: Ruben
authors.initials: R
authors.lastname: Carrasco
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
authors.forename: Steven P
authors.initials: SP
authors.lastname: Treon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics; D019075:Electrophoresis, Capillary; D005260:Female; D015870:Gene Expression; D005809:Genes, Regulator; D006801:Humans; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics* / Q000473:pathology