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

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.

Keywords::

• MZB1
• gene expression
• survival
• lymphoma

Acknowledgements

The authors would like to thank the Laboratory for Leukemia Diagnostics for providing microarray data and patient samples, especially Claudia and Torsten Haferlach, Frank Dicker, Alexander Kohlmann and Susanne Schnittger. In addition we thank Natalia Kerber and Evelyn Zellmeier for assistance in sample processing.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

T. Herold was supported by the K. L. Weigand'schen Stiftung, the Curt-Bohnewands-Fonds and the Georg und Traud Gravenhorst – Stiftung and by the Deutsche Forschungsgemeinschaft, Collaborative Research Center 684 “Molecular mechanisms of normal and malignant hematopoiesis” (S. K. Bohlander). This work was supported by a grant from the German Ministry of Education and Research (BMBF; 01GS0876) to C. Buske and S. K. Bohlander. V. Jurinovic was supported by the German José Carreras Leukaemia Foundation (DJCLS H06/04V) and the BMBF medical systems biology project HaematoSYS (BMBF-FKZ 03415452I).