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Mechanism of action of lenalidomide in hematological malignancies

Venumadhav Kotla1, Swati Goel1, Sangeeta Nischal1, Christoph Heuck1, Kumar Vivek2, Bhaskar Das3 and Amit Verma1*

Author Affiliations

1 Department of Medicine, Albert Einstein College of Medicine, Bronx, USA

2 Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, USA

3 Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, USA

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Journal of Hematology & Oncology 2009, 2:36  doi:10.1186/1756-8722-2-36

Published: 12 August 2009


Immunomodulatory drugs lenalidomide and pomalidomide are synthetic compounds derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. Lenalidomide is a 4-amino-glutamyl analogue of thalidomide that lacks the neurologic side effects of sedation and neuropathy and has emerged as a drug with activity against various hematological and solid malignancies. It is approved by FDA for clinical use in myelodysplastic syndromes with deletion of chromosome 5q and multiple myeloma. Lenalidomide has been shown to be an immunomodulator, affecting both cellular and humoral limbs of the immune system. It has also been shown to have anti-angiogenic properties. Newer studies demonstrate its effects on signal transduction that can partly explain its selective efficacy in subsets of MDS. Even though the exact molecular targets of lenalidomide are not well known, its activity across a spectrum of neoplastic conditions highlights the possibility of multiple target sites of action.