Genetic and Transcript Changesin Cereblon in IMiD-Treated Myeloma Patients
نویسندگان
چکیده
منابع مشابه
High cereblon expression is associated with better survival in patients with newly diagnosed multiple myeloma treated with thalidomide maintenance.
Recently, cereblon (CRBN) expression was found to be essential for the activity of thalidomide and lenalidomide. In the present study, we investigated whether the clinical efficacy of thalidomide in multiple myeloma is associated with CRBN expression in myeloma cells. Patients with newly diagnosed multiple myeloma were included in the HOVON-65/GMMG-HD4 trial, in which postintensification treatm...
متن کاملMouse Monoclonal Antibodies Generated from Full Length Human Cereblon: Detection of Cereblon Protein in Patients with Multiple Myeloma
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 ...
متن کاملModulation of cereblon levels by anti-myeloma agents.
The use of thalidomide derivatives (IMIDs) has improved multiple myeloma prognosis, through an unknown mechanism of action. Recently one molecular target, the cereblon (CRBN) protein, has been identified. CRBN acts by binding to DDB1-CUL4-ROC1 forming a ubiquitin ligase multiprotein complex. We have generated antibodies to different regions of CRBN protein, and analyzed the biological consequen...
متن کاملRole of IRF4 in resistance to immunomodulatory (IMid) compounds® in Waldenström’s macroglobulinemia
Background Immunomodulatory drugs, IMid compounds, are active in Waldenström's macroglobulinemia (WM), although in a lesser extent than multiple myeloma, where it was initially developed. We hypothesized WM tumour cells might develop mechanisms of resistance, and sought to identify and describe these mechanisms. Material and Method MM and WM-derived cell lines, and Waldenström's CD19+ cells w...
متن کاملCereblon and Its Role in the Treatment of Multiple Myeloma by Lenalidomide or Pomalidomide
Cereblon (CRBN) is part of the cullin 4-containing E3 ubiquitin ligase complex (CRL4) and functions as a target of thalidomide and its analogs (lenalidomide and pomalidomide) known as immunomodulatory drugs (IMiDs). The CRBN gene consists of 1329 base pairs, 11 exons, and encodes a protein of 443 amino acids. Exons 10-11 code for the binding site of IMiDs and exons 5-7 for the binding site of D...
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ژورنال
عنوان ژورنال: Blood
سال: 2019
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood-2019-126828