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The emergence of resistance to all available treatments is a major challenge in improving survival in myeloma patients.
Cereblon (CRBN) is a widely used IMiD and new CelMOD drug in myeloma, as well as an essential binding protein for certain PROTACs being developed for a variety of diseases. Using genome-wide sequencing data from 455 patients and RNA sequencing data from 655 patients,
found that three CRBN variants (i.e., point mutations, copy number loss/structural variation, and special transcription variants (such as exon 10 shear variants) gradually increased in frequency, accompanied by IMiD sexual exposure until about one-third of patients with POM incurability developed.
researchers found that all three CRBN variants were associated with poor use of POM in patients with LEN retrebility, including previously unexpiced individuals with missing copies and structural variations.
, it is understood that this study is the first comprehensive analysis of the CBRN mutation in patients with myeloma progressing in treatment, which can help guide patients to choose CRBN targeted drug sequentia therapy.
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