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High expression of cereblon ( CRBN ) is associated with improved clinical response in patients with multiple myeloma treated with lenalidomide and dexamethasone
Author(s) -
Heintel Daniel,
Rocci Alberto,
Ludwig Heinz,
Bolomsky Arnold,
Caltagirone Simona,
Schreder Martin,
Pfeifer Sabine,
Gisslinger Heinz,
Zojer Niklas,
Jäger Ulrich,
Palumbo Antonio
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12338
Subject(s) - cereblon , lenalidomide , multiple myeloma , medicine , dexamethasone , oncology , immunology , biology , ubiquitin ligase , biochemistry , ubiquitin , gene
Summary Cereblon ( CRBN ) has recently been identified as a target for immunomodulatory drugs ( IM i D s) 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 ( IRF 4 ) ( P < 0·001) and with CTNNB 1 ( 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 IRF 4 , which is an important target of IM i D therapy.