title: High expression of cereblon (CRBN) is associated with improved clinical response in patients with multiple myeloma treated with lenalidomide and dexamethasone.
abstract: Cereblon (CRBN) has recently been identified as a target for immunomodulatory drugs (IMiDs) and its downregulation has been linked to resistance to lenalidomide. Here, we studied CRBN expression by real time polymerase chain reaction in 49 bone marrow samples of newly diagnosed patients with multiple myeloma treated with lenalidomide and dexamethasone. Median CRBN expression was 3·45 in patients who achieved complete response, and 3·75, 2·01, 0·78, and 0·70 in those with very good partial response, partial response, stable disease and progressive disease respectively. CRBN expression levels correlated significantly with response to lenalidomide treatment (r = 0·48; P < 0·001). Among established prognostic parameters, only beta-2-microglobulin correlated with cereblon (r = 0·66; P < 0·001). A close association of CRBN with interferon regulatory factor 4 (IRF4) (P < 0·001) and with CTNNB1 (P < 0·001) was found. Overall, a statistically significant association between baseline CRBN expression and response in MM patients treated with lenalidomide is shown. CRBN expression is closely associated with IRF4, which is an important target of IMiD therapy.
authors.affiliation: Department of Internal Medicine I, Center for Oncology and Haematology, Wilhelminenspital, Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Heintel
authors.affiliation: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Ospedale Molinette, Torino, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rocci
authors.affiliation: Department of Internal Medicine I, Center for Oncology and Haematology, Wilhelminenspital, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.affiliation: Department of Internal Medicine I, Center for Oncology and Haematology, Wilhelminenspital, Vienna, Austria.
authors.forename: Arnold
authors.initials: A
authors.lastname: Bolomsky
authors.affiliation: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Ospedale Molinette, Torino, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Caltagirone
authors.affiliation: Department of Internal Medicine I, Center for Oncology and Haematology, Wilhelminenspital, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Schreder
authors.affiliation: Department of Internal Medicine I, Center for Oncology and Haematology, Wilhelminenspital, Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pfeifer
authors.affiliation: Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna (MUW), Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
authors.affiliation: Department of Internal Medicine I, Center for Oncology and Haematology, Wilhelminenspital, Vienna, Austria.
authors.forename: Niklas
authors.initials: N
authors.lastname: Zojer
authors.affiliation: Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna (MUW), Vienna, Austria.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jäger
authors.affiliation: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Ospedale Molinette, Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001853:Bone Marrow / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D006801:Humans; D050835:Interferon Regulatory Factors / Q000096:biosynthesis; D000077269:Lenalidomide; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010447:Peptide Hydrolases / Q000096:biosynthesis*; D010950:Plasma Cells / Q000378:metabolism; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012189:Retrospective Studies; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D051176:beta Catenin / Q000096:biosynthesis; D000099218:Interferon Regulatory Factor-4
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D003907:Dexamethasone; D050835:Interferon Regulatory Factors; D000077269:Lenalidomide; D009363:Neoplasm Proteins; D010447:Peptide Hydrolases; D013792:Thalidomide; D044767:Ubiquitin-Protein Ligases; D051176:beta Catenin; D000099218:Interferon Regulatory Factor-4; C502543:CRBN protein, human; C495270:CTNNB1 protein, human
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