Association of CRBN Gene with Immunomodulatory Drug Resis- tance in Multiple Myeloma.
10.7534/j.issn.1009-2137.2015.03.056
- Author:
Qian-Qian CAI
1
;
Jian LI
2
Author Information
1. Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China.
2. Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China. E-mail: pumch.li.jian@gmail.com.
- Publication Type:Journal Article
- MeSH:
Drug Resistance, Neoplasm;
Humans;
Immunosuppressive Agents;
Multiple Myeloma;
Peptide Hydrolases;
Prognosis;
Proteasome Endopeptidase Complex;
Transcription Factors
- From:
Journal of Experimental Hematology
2015;23(3):892-897
- CountryChina
- Language:Chinese
-
Abstract:
Human CRBN (cereblon) gene is located on chromosome 3 at 3p26 and its encoding protein is a member of E3 ubiquitin ligase complex (composed of CRBN, DDB1, CUL4A and ROC1). The E3 ubiquitin ligase complex functions in the ubiquitin-proteasome protein degradation pathway and attaches polyubiquitin chains to substrate proteins for degradation via the protease complex. Currently, there are no standardized assays for CRBN gene and protein measurement although quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry and Western blot are widely used. CRBN has been identified as a direct target for immunomodulatory drugs (IMiD) and plays a significant role in anti-proliferation, pro-apoptotic effects, anti-angiogenic activities, immunomodulatory activities and intervention of cell surface adhesion molecules between myeloma cells and bone marrow stromal cells. Recently, clinical data show that majority of the multiple myeloma patients treated with IMiD develop drug-resistance over time by unknown mechanisms. Fortunately, various in vivo and in vitro studies have revealed that the decreased CRBN expression or CRBN deletion is associated with resistance to IMiD in treating multiple myeloma, and CRBN expression levels may have a prognostic significance. Furthermore, the most recently discovered protein IKZF1, IKZF3, IRF4, C/EBPβ and Wnt/catenin signaling pathways may also be closely related to IMiD resistance in myeloma.
