PuSH - Publikationsserver des Helmholtz Zentrums München: High expression of <em>MZB1</em> predicts adverse prognosis in chronic lymphocytic leukemia, follicular lymphoma and diffuse large B-cell lymphoma and is associated with a unique gene expression signature.

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Herold, T. ; Mulaw, M.A. ; Jurinovic, V.* ; Seiler, T. ; Metzeler, K.H.* ; Dufour, A.* ; Schneider, S.* ; Kakadia, P.M. ; Spiekermann, K. ; Mansmann, U.* ; Hiddemann, W. ; Buske, C.* ; Dreyling, M. ; Bohlander, S.K.

High expression of MZB1 predicts adverse prognosis in chronic lymphocytic leukemia, follicular lymphoma and diffuse large B-cell lymphoma and is associated with a unique gene expression signature.

Leuk. Lymphoma 54, 1652-1657 (2013)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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We recently identified the marginal zone B and B1 cellspecific protein ( MZB1 ) as part of a gene expression signature associated with outcomes in chronic lymphocytic leukemia (CLL). MZB1 is important for B cell function as a key regulator of antibody secretion, calcium homeostasis and adhesion. Therefore, we analyzed the role of MZB1 expression levels in 139 patients with CLL using quantitative real-time polymerase chain reaction (qRT-PCR) and microarray data sets in CLL, follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM) and acute myeloid leukemia (AML). High MZB1 expression was associated with inferior survival in CLL (hazard ratio [HR]: 1.63 [confidence interval (CI): 1.14 – 2.33], p 0.007), FL (221286_s_at HR: 1.16 [CI: 0.98 – 1.37], p 0.086; 223565_at: HR: 1.3 [CI: 1.1 – 1.61], p 0.015) and DLBCL (221286_s_at: HR: 1.17 [CI: 1.06 – 1.3], p 0.003; 223565_at: HR: 1.21 [CI: 1.08 – 1.35], p 0.001). In DLBCL MZB1 expression was an additive prognostic marker in a multivariate model including activated B-cell like (ABC) versus germinal center (GCB) subtype. Additionally, MZB1 expression correlated with a unique gene expression pattern. This study is the first to show that the expression level of a single gene has prognostic significance in different lymphoma subtypes. Due to its biological function, MZB1 may play a central role in B cell neoplasms and is a potential target for future therapeutic interventions.

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