Expression of regulatory genes for lymphoplasmacytic cell differentiation in Waldenstrom Macroglobulinemia.
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.
Leleu
Xavier
X
Bing Center for Waldenstrom's Macroglobulinemia and Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Hunter
Zachary R
ZR
Xu
Lian
L
Roccaro
Aldo M
AM
Moreau
Anne-Sophie
AS
Santos
Daniel D
DD
Hatjiharissi
Evdoxia
E
Bakthavachalam
Vinod
V
Adamia
Sophia
S
Ho
Allen W
AW
Soumerai
Jacob
J
Patterson
Christopher J
CJ
Manning
Robert J
RJ
Hamilton
Susanna
S
Verselis
Sigitas
S
Fox
Edward
E
Carrasco
Ruben
R
Ghobrial
Irene M
IM
Treon
Steven P
SP
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