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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Expression of CRBN, IKZF1, and IKZF3 does not predict lenalidomide sensitivity and mutations in the cereblon pathway are infrequent in multiple myeloma

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Genetic polymorphisms in genes of class switch recombination and multiple myeloma risk and survival: an IMMEnSE study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Clinical prognostic scores are poor predictors of overall survival in various types of malignant lymphomas

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. International multicentre retrospective cohort study of ocular adnexal marginal zone B-cell lymphoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Epigenetic therapy in hematological cancers

    Research output: Contribution to journalReviewResearchpeer-review

  4. Blodsygdomme

    Research output: Chapter in Book/Report/Conference proceedingBook chapterEducationpeer-review

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The immunomodulatory drug thalidomide, and its analogs, lenalidomide, and pomalidomide (IMiDs), have become essential components of the standard treatment for multiple myeloma (MM), and have led to significant improvement of survival in patients with this devastating disease. Cereblon (CRBN), the direct target of IMiDs, has been proposed as a predictive biomarker of response to IMiDs. Using standard immunohistochemistry in formalin-fixed paraffin embedded (FFPE) bone marrow samples of 23 patients treated with a lenalidomide-containing regimen, we found that the malignant plasma cells of all the patients stained positive for CRBN, IKZF1, and IKZF3, regardless of sensitivity to IMiDs. Moreover, we detected no mutations in CRBN, IKZF1, IKZF3, CUL4A, or IRF4, but found expanded TP53-mutated clones in two out of seven sequential samples. Thus, our data argue against the use of CRBN and its downstream targets as predictive biomarkers of IMiD response in MM and confirm clonal evolution patterns during lenalidomide resistance.

Original languageEnglish
JournalLeukemia and Lymphoma
Pages (from-to)180-188
Number of pages9
ISSN1042-8194
DOIs
Publication statusPublished - 2 May 2018

ID: 54781628