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. 2013 Aug;54(8):1652-7. doi: 10.3109/10428194.2012.753445. Epub 2012 Dec 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Cytokines / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Lymphoma, Follicular / genetics*
  • Lymphoma, Follicular / mortality
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Multiple Myeloma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Prognosis
  • Transcriptome*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • MZB1 protein, human