Blood: CBRN multiple mutations associated with multiple myeloma and drug resistance to lysamine or pomadamine.

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 CellMOD drug for myeloma and an essential binding protein for certain PROTACs that are being developed for a variety of diseases. Using genome-wide sequencing data from 455 patients and RNA sequencing data from 655 patients,
found that the frequency of three CRBN variants (i.e., point mutations, missing copies/structural variations, and special transcript variations (e.g., exogenation 10 shear variations)) increased gradually, with sexual exposure of IMiD until approximately one-third of the progressions were CBRN variants in patients where POM was difficult to treat.
the researchers found that all three CRBN variants were associated with poor POM treatment in patients with LEN incurable patients, including individuals who had not previously studied the number of copies they carried and structural variations.
it is understood that this study is the first comprehensive analysis of CBRN variation in patients with myeloma who are progressing in treatment, which can help guide patients to choose the sequence therapy of CRBN-targeted drugs.
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