- Title
- Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients
- Creator
- Chan, Angela; Neeson, Paul; Leeansyah, Edwin; Tainton, K.; Quach, Hang; Prince, Henry; Godfrey, Dale; Ritchie, David; Berzins, Stuart
- Date
- 2010
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/103184
- Identifier
- vital:10852
- Identifier
-
https://doi.org/10.1038/leu.2009.279
- Identifier
- ISSN:08876924
- 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. © 2010 Macmillan Publishers Limited All rights reserved.
- Relation
- Leukemia Vol. 24, no. 3 (2010), p. 592-600
- Rights
- Copyright Macmillan
- Rights
- This metadata is freely available under a CCO license
- Subject
- Lenalidomide; Myelodysplastic syndrome; NKT cells; Gamma interferon; Tumor necrosis factor; Adult; Aged; CD4+ T lymphocyte; CD8+ T lymphocyte; Cell compartmentalization; Cell function; Cell proliferation; Clinical article; Clinical trial; Controlled clinical trial; Controlled study; Cytokine production; Drug efficacy; Female; Human; Human cell; Lymphocyte count; Male; Multiple cycle treatment; Natural killer cell; Peripheral blood mononuclear cell; Priority journal; Treatment duration; Treatment response; Aged, 80 and over; Antigens, CD3; Antineoplastic Agents; Cytokines; Humans; Longitudinal Studies; Middle Aged; Myelodysplastic Syndromes; Natural Killer T-Cells; Thalidomide; 1103 Clinical Sciences; 1112 Oncology and Carcinogenesis
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