title: [Association of CRBN Gene with Immunomodulatory Drug Resis- tance in Multiple Myeloma].
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.
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007166:Immunosuppressive Agents; D009101:Multiple Myeloma; D010447:Peptide Hydrolases; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C502543:CRBN protein, human; D007166:Immunosuppressive Agents; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex