title: 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.
abstract: Abstract We recently identified the marginal zone B and B1 cell-specific 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.
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany. bohlander@helmholtz-muenchen.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Herold
authors.forename: Medhanie A
authors.initials: MA
authors.lastname: Mulaw
authors.forename: Vindi
authors.initials: V
authors.lastname: Jurinovic
authors.forename: Till
authors.initials: T
authors.lastname: Seiler
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Metzeler
authors.forename: Annika
authors.initials: A
authors.lastname: Dufour
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schneider
authors.forename: Purvi M
authors.initials: PM
authors.lastname: Kakadia
authors.forename: Karsten
authors.initials: K
authors.lastname: Spiekermann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Christian
authors.initials: C
authors.lastname: Buske
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Bohlander
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality; D009101:Multiple Myeloma / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D011379:Prognosis; D059467:Transcriptome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; C434482:MZB1 protein, human