TY - JOUR
T1 - Mouse monoclonal antibodies generated from full length human cereblon
T2 - Detection of cereblon protein in patients with multiple myeloma
AU - Chang, Xiubao
AU - Xu, Qinqin
AU - Hou, Yuexian
AU - Li, Cynthia
AU - Xu, Ye
AU - Stewart, A. Keith
N1 - Funding Information:
Acknowledgments: The authors thank Leah Moore for participating in manuscript preparation; Lou A. Gross (Pathology Research Core in Rochester) and Ryan S. Robetorye (Pathology Core in Scottsdale) for participating in immunohistochemistry staining of MM patients’ specimens; This work was partially supported by the grant (6408-14) from Leukemia & Lymphoma Society Xiubao Chang.
Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2017/9/17
Y1 - 2017/9/17
N2 - Immunomodulatory drugs (IMiDs) are profoundly active compounds in the treatment of patients with multiple myeloma (MM). However, despite the fact that treatment with IMiDs has dramatically improved survival for patients with MM, the majority of MM patients develop IMiDs resistance over time. We have found that expression of functional cereblon is required for IMiDs’ action. In addition, it has been reported that cells expressing high levels of cereblon are resistant to proteasome inhibitor, implying that patients with high levels of cereblon should be resistant to proteasome inhibitor. If the above conclusions are correct, cereblon could be considered as a biomarker to determine which standard regimens should be used to treat patients with MM. Unfortunately, the conclusions mentioned above have not been clinically confirmed. In order to confirm these conclusions, we have generated three highly specific mouse monoclonal antibodies (mAbs) against full-length human cereblon. These mAbs can be used to do western blot, immunoprecipitation and immunohistochemistry staining. In addition, their epitopes have been precisely determined and the peptides covering their epitopes completely blocked the antibody binding to cereblon in western blot analysis or in immunohistochemistry staining of MM patients’ specimens.
AB - Immunomodulatory drugs (IMiDs) are profoundly active compounds in the treatment of patients with multiple myeloma (MM). However, despite the fact that treatment with IMiDs has dramatically improved survival for patients with MM, the majority of MM patients develop IMiDs resistance over time. We have found that expression of functional cereblon is required for IMiDs’ action. In addition, it has been reported that cells expressing high levels of cereblon are resistant to proteasome inhibitor, implying that patients with high levels of cereblon should be resistant to proteasome inhibitor. If the above conclusions are correct, cereblon could be considered as a biomarker to determine which standard regimens should be used to treat patients with MM. Unfortunately, the conclusions mentioned above have not been clinically confirmed. In order to confirm these conclusions, we have generated three highly specific mouse monoclonal antibodies (mAbs) against full-length human cereblon. These mAbs can be used to do western blot, immunoprecipitation and immunohistochemistry staining. In addition, their epitopes have been precisely determined and the peptides covering their epitopes completely blocked the antibody binding to cereblon in western blot analysis or in immunohistochemistry staining of MM patients’ specimens.
KW - Cereblon (CRBN)
KW - Epitope
KW - Immunohistochemistry (IHC) staining
KW - Immunomodulatory drugs (IMiDs)
KW - Immunoprecipitation
KW - Monoclonal antibody (mAb)
KW - Multiple myeloma (MM)
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U2 - 10.3390/ijms18091999
DO - 10.3390/ijms18091999
M3 - Article
C2 - 28926977
AN - SCOPUS:85029668601
VL - 18
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 9
M1 - 1999
ER -