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Immunology

Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

Abstract

Myelodysplastic syndrome (MDS) comprises a group of clonal bone marrow disorders characterized by ineffective hematopoiesis and increased predisposition to acute myeloid leukemia. The causes of MDS remain poorly defined, but several studies have reported the NKT cell compartment of patients with MDS is deficient in number and functionally defective. In support of a central role for NKT cells, a pilot clinical study reported that lenalidomide (an approved treatment for MDS) increased NKT cell numbers in patients with MDS, and several in vitro studies showed lenalidomide specifically promoted NKT cell proliferation and cytokine production. We tested this in a much larger study and confirm a moderate in vitro augmentation of some NKT cell functions by lenalidomide, but find no impact on the NKT cell compartment of patients treated with lenalidomide, despite a consistently positive clinical response. We further show that the frequency and cytokine production of NKT cells is normal in patients with MDS before treatment and remains stable throughout 10 months of lenalidomide therapy. Collectively, our data challenge the concept that NKT cell defects contribute to the development of MDS, and show that a clinical response to lenalidomide is not dependent on modulation of NKT cell frequency or function.

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Acknowledgements

We gratefully acknowledge the participation of patients and blood donors in the study, and the contributions of Sharyn Meadows and Amanda Marshall (research nurses), Dirk Honemann and Melita Kenealy (clinical fellows), Rhonda Holdsworth (Australian Red Cross Blood Bank) and Kon Kyparissoudis (research assistant). We acknowledge the generous funding of this study by the National Health and Medical Research Council (NHMRC), Project Grant (No. 454363). We also acknowledge the following funding support: SPB is supported by an NHMRC Career Development Award ; DIG is supported by an NHMRC Program Grant (No. 251608, renewed as No. 454569) and an NHMRC Research Fellowship.

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Correspondence to S P Berzins.

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Chan, A., Neeson, P., Leeansyah, E. et al. Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients. Leukemia 24, 592–600 (2010). https://doi.org/10.1038/leu.2009.279

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