title: The clinical significance of cereblon expression in multiple myeloma.
abstract: Cereblon (CRBN) mediates immunomodulatory drug (IMiD) action in multiple myeloma (MM). We demonstrate here that no patient with very low CRBN expression responded to IMiD plus dexamethasone therapy. In 53 refractory MM patients treated with pomalidomide and dexamethasone, CRBN levels predict for decreased response rates and significant differences in PFS (3.0 vs. 8.9 months, p<0.001) and OS (9.1 vs. 27.2 months, p=0.01) (lowest quartile vs. highest three quartiles). While higher CRBN levels can serve as a surrogate for low risk disease, our study demonstrates that low CRBN expression can predict resistance to IMiD monotherapy and is a predictive biomarker for survival outcomes.
authors.affiliation: Cancer Care and Hematology, University of Colorado Health, Fort Collins, CO, USA. Electronic address: Steven.Schuster@UCHealth.org.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Schuster
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: K Martin
authors.initials: KM
authors.lastname: Kortuem
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: Yuan Xiao
authors.initials: YX
authors.lastname: Zhu
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: Esteban
authors.initials: E
authors.lastname: Braggio
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: Chang-Xin
authors.initials: CX
authors.lastname: Shi
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Bruins
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Schmidt
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Ahmann
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Shaji
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Mikhael
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Betsy
authors.initials: B
authors.lastname: Laplant
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: Mia D
authors.initials: MD
authors.lastname: Champion
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Laumann
authors.affiliation: Department of Hematology, University of Arkansas, Little Rock, AR, USA.
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: P Leif
authors.initials: PL
authors.lastname: Bergsagel
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Lacy
authors.affiliation: Division of Hematology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010447:Peptide Hydrolases / Q000235:genetics*; D011379:Prognosis; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome; D044767:Ubiquitin-Protein Ligases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C502543:CRBN protein, human; D013792:Thalidomide; D003907:Dexamethasone; C467566:pomalidomide; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases
keywords: Biological markers; Cereblon; Gene expression profiling; Immunomodulatory drugs; Multiple myeloma