Expression of cereblon protein assessed by immunohistochemicalstaining in myeloma cells is associated with superior response of thalidomide- and lenalidomide-based treatment, ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-08

AUTHORS

Shang-Yi Huang, Chung-Wu Lin, Hsiu-Hsia Lin, Ming Yao, Jih-Luh Tang, Shang-Ju Wu, Yao-Chang Chen, Hsiao-Yun Lu, Hsin-An Hou, Chien-Yuan Chen, Wen-Chien Chou, Woei Tsay, Sheng-Je Chou, Hwei-Fang Tien

ABSTRACT

Cereblon (CRBN) is essential for the anti-myeloma (MM) activity of immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide. However, the clinical implications of CRBN in MM patients are unclear. Using immunohistochemical (IHC) staining on paraffin-embedded bone marrow sections, the expression of CRBN protein in myeloma cells (MCs) was assessed in 40 relapsed/refractory MM (RRMM) patients who received lenalidomide/dexamethasone (LD) and 45 and 22 newly diagnosed MM (NDMM) patients who received thalidomide/dexamethasone (TD) and melphalan/bortezomib/prednisolone (MVP), respectively. IHC staining were scored on a scale representing the diffuseness and intensity of positive-staining MCs (range, 0-8) and a score ≥4.5 was used for CRBN positivity (CRBN(+)) on a cut-point analysis of all possible scores and response of TD and LD. Compared to CRBN(+) NDMM patients, CRBN(-) NDMM patients had more international staging system (ISS) III (26 vs. 61 %, respectively; P = 0.006). In the LD and TD cohorts, the response rate (RR) was higher in CRBN(+) patients than CRBN(-) patients (LD 79 vs. 33 %, respectively; P = 0.005) (TD 75 vs. 29 %, respectively; P = 0.005); however, this trend was not observed in the MVP cohort. In the LD and TD cohorts, the positive and negative prediction value of CRBN(+) for treatment response was 79 and 67 % and 75 and 71 %, respectively. Multivariate analysis showed that CRBN(+) was a significant factor associated with superior RR for LD and TD. The data suggest that expression of CRBN protein in MCs assessed using the IHC is a feasible approach to predict the response of IMiDs in MM patients. More... »

PAGES

1371-1380

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00277-014-2063-7

DOI

http://dx.doi.org/10.1007/s00277-014-2063-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1045743616

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24687382


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