Science and research

Cereblon Expression in Lower-Risk Myelodysplastic Syndromes

The effect of immunomodulatory or cereblon binding drug lenalidomide in the treatment of anemic transfusion-dependent MDS patients with isolated 5q deletion [del(5q)] is established, but precise cellular targets and molecular mechanisms of this drug in patients with MDS remain unclear.

To gain insight into the role of cereblon (CRBN) gene expression in lower risk MDS with or without del(5q) and into the mechanism of lenalidomide action we studied CRBN expression in lower risk MDS patients with or without del(5q). The highest CRBN mRNA levels were detected in MDS patients with del(5q) in comparison with patients with normal chromosome 5 and with healthy controls. A significant downregulation of CRBN expression during lenalidomide treatment is associated with resistance to the lenalidomide similarly to the treatment of multiple myeloma. However, the target of ubiquitination and degradation by cullin4 E3 ubiquitin ligase containing cereblon as substrate receptor is different in multiple myeloma (Ikaros transcription factors IKZF1 and IKZF3) and in MDS with del(5q) (casein kinase 1α).

The study of this mechanism and its importance also in lower risk MDS patients with normal chromosome 5, alternative splicing of cereblon pre mRNA variants and the role of polymorphism in the cereblon gene is under investigation.

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Ústav hematologie a krevní transfuze
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