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Int. J. Mol. Sci. 2017, 18(9), 1999; doi:10.3390/ijms18091999

Mouse Monoclonal Antibodies Generated from Full Length Human Cereblon: Detection of Cereblon Protein in Patients with Multiple Myeloma

1
Department of Biochemistry & Molecular Biology, College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
2
Division of Hematology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 22 August 2017 / Revised: 11 September 2017 / Accepted: 13 September 2017 / Published: 17 September 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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. View Full-Text
Keywords: multiple myeloma (MM); cereblon (CRBN); monoclonal antibody (mAb); epitope; immunohistochemistry (IHC) staining; immunoprecipitation; immunomodulatory drugs (IMiDs) multiple myeloma (MM); cereblon (CRBN); monoclonal antibody (mAb); epitope; immunohistochemistry (IHC) staining; immunoprecipitation; immunomodulatory drugs (IMiDs)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Chang, X.; Xu, Q.; Hou, Y.; Li, C.; Xu, Y.; Stewart, A.K. Mouse Monoclonal Antibodies Generated from Full Length Human Cereblon: Detection of Cereblon Protein in Patients with Multiple Myeloma. Int. J. Mol. Sci. 2017, 18, 1999.

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