USP9X stabilizes XIAP to regulate mitotic cell death and chemoresistance in aggressive B-cell lymphoma.
GLA - German Lymphoma Alliance

Abstract (Expand)

The mitotic spindle assembly checkpoint (SAC) maintains genome stability and marks an important target for antineoplastic therapies. However, it has remained unclear how cells execute cell fate decisions … under conditions of SAC-induced mitotic arrest. Here, we identify USP9X as the mitotic deubiquitinase of the X-linked inhibitor of apoptosis protein (XIAP) and demonstrate that deubiquitylation and stabilization of XIAP by USP9X lead to increased resistance toward mitotic spindle poisons. We find that primary human aggressive B-cell lymphoma samples exhibit high USP9X expression that correlate with XIAP overexpression. We show that high USP9X/XIAP expression is associated with shorter event-free survival in patients treated with spindle poison-containing chemotherapy. Accordingly, aggressive B-cell lymphoma lines with USP9X and associated XIAP overexpression exhibit increased chemoresistance, reversed by specific inhibition of either USP9X or XIAP. Moreover, knockdown of USP9X or XIAP significantly delays lymphoma development and increases sensitivity to spindle poisons in a murine Emu-Myc lymphoma model. Together, we specify the USP9X-XIAP axis as a regulator of the mitotic cell fate decision and propose that USP9X and XIAP are potential prognostic biomarkers and therapeutic targets in aggressive B-cell lymphoma.

Authors: K. Engel, M. Rudelius, J. Slawska, L. Jacobs, B. Ahangarian Abhari, B. Altmann, J. Kurutz, A. Rathakrishnan, V. Fernandez-Saiz, A. Brunner, B. S. Targosz, F. Loewecke, C. J. Gloeckner, M. Ueffing, S. Fulda, M. Pfreundschuh, L. Trumper, W. Klapper, U. Keller, P. J. Jost, A. Rosenwald, C. Peschel, F. Bassermann

Date Published: 19th Jun 2016

Publication Type: Not specified

Human Diseases: B-cell lymphoma

SOM Analysis of 873 Malignant Lymphomas
MMML-MYC-SYS

We present a transcriptome map of mature B-cell lymphomas that was obtained by analyzing expression data of 873 biopsy specimens including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt’s lymphoma (BL), mixed FL/DLBCL lymphomas, primary mediastinal large B-cell lymphoma (PMBL), multiple myeloma (MM), IRF4-rearranged large cell lymphoma, MYC-negative high-grade B-cell lymphomas with Chr. 11q aberration pattern (mnBLL-11q), and Mantle cell lymphoma (MCL) to describe their ...

Creator: Henry Löffler-Wirth

Submitters: Christoph Beger, Henry Löffler-Wirth

Data file type: SOM Data

External Link
SOM Analysis of 221 Malignant Lymphomas
MMML-MYC-SYS

We performed gene-expression analysis of 220 mature aggressive B-cell lymphomas, including a core group of 8 Burkitt's lymphomas that met all World Health Organization (WHO) criteria. A SOM was trained using molecular classification of specimen according to molecular Burkitt's Lymphoma score provided by Hummel et al.

Creator: Henry Löffler-Wirth

Submitters: Christoph Beger, Henry Löffler-Wirth

Data file type: SOM Data

External Link

Navigate

Health Atlas - Local Data Hub/Leipzig

The Health Atlas - Local Data Hub/Leipzig is an alliance of medical ontologists, medical systems biologists and clinical trials groups to design and implement a multi-functional and quality-assured atlas. It provides models, data and metadata on specific use cases from medical research fields.

Registered Repository

re3data.org Badge
Powered by
 (v.1.13.0-master)
Health Atlas | Funding and Programmes | Credits | Terms & Conditions | Privacy Policy | Imprint
Copyright © 2008 - 2021 The University of Manchester and HITS gGmbH
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig

By continuing to use this site you agree to the use of cookies