Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients
Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients
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DOI：
10.1038/leu.2009.279
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发表时间：
2010-03-01
期刊：
影响因子：
11.4
通讯作者：
Berzins, S. P.
中科院分区：
文献类型：
--
作者：
Chan, A. C.;Neeson, P.;Berzins, S. P.
骨髓增生异常综合征（MDS）包括一组克隆性骨髓疾病，其特征是造血功能低下和急性髓系白血病易感性增加。MDS的病因仍不明确，但一些研究报道了MDS患者的NKT细胞室数量不足和功能缺陷。为了支持NKT细胞的核心作用，一项试点临床研究报告说，来那度胺（一种被批准的MDS治疗药物）增加了MDS患者的NKT细胞数量，几项体外研究显示来那度胺特异性地促进了NKT细胞增殖和细胞因子的产生。我们在一项更大的研究中对此进行了测试，并证实来那度胺在体外适度增强了一些NKT细胞的功能，但发现来那度胺对NKT细胞室没有影响，尽管临床反应一直是积极的。我们进一步表明，在MDS患者治疗前，NKT细胞的频率和细胞因子的产生是正常的，并在来那度胺治疗的10个月期间保持稳定。总的来说，我们的数据挑战了NKT细胞缺陷导致MDS发展的概念，并表明来那度胺的临床反应不依赖于NKT细胞频率或功能的调节。白血病（2010）24,592-600；doi: 10.1038 / leu.2009.279;2010年1月14日在线发布
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. Leukemia (2010) 24, 592-600; doi:10.1038/leu.2009.279; published online 14 January 2010