National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC), Center for Cell Therapy (CTC) and Regional Blood Center, Faculty of Medicine (FMRP), University of São Paulo (USP), Rua Tenente Catão Roxo, 2.501, Bairro Monte Alegre, Campus Universitário, Ribeirão Preto, São Paulo, 14051-140, Brazil,
Ann Hematol. 2014 Sep;93(9):1457-65. doi: 10.1007/s00277-014-2066-4. Epub 2014 Apr 3.
Recent studies have demonstrated the role of adenosine (ADO) in sickle-cell anemia (SCA). ADO is produced by CD39 and CD73 and converted to inosine by adenosine deaminase (ADA). We evaluated the effects of hydroxycarbamide (HU) treatment on the modulation of adenosine levels in SCA patients. The expressions of CD39, CD73, and CD26 were evaluated by flow cytometry on blood cells in 15 HU-treated and 17 untreated patients and 10 healthy individuals. RNA was extracted from monocytes, and ADA gene expression was quantified by real-time PCR. ADA activity was also evaluated. We found that ADA transcripts were two times higher in monocytes of HU-treated patients, compared with untreated (P = 0.039). Monocytes of HU-treated patients expressed CD26, while monocytes of controls and untreated patients did not (P = 0.023). In treated patients, a lower percentage of T lymphocytes expressed CD39 compared with untreated (P = 0.003), and the percentage of T regulatory (Treg) cells was reduced in the treated group compared with untreated (P = 0.017) and controls (P = 0.0009). Besides, HU-treated patients displayed increased ADA activity, compared with untreated. Our results indicate a novel mechanism of action of HU mediated by the reduction of adenosine levels and its effects on pathophysiological processes in SCA.
最近的研究表明，腺苷（ADO）在镰状细胞贫血（SCA）中发挥作用。ADO 由 CD39 和 CD73 产生，并由腺苷脱氨酶（ADA）转化为肌苷。我们评估了羟基脲（HU）治疗对 SCA 患者腺苷水平调节的影响。通过流式细胞术评估了 15 例 HU 治疗和 17 例未治疗患者以及 10 名健康个体的血细胞中 CD39、CD73 和 CD26 的表达。从单核细胞中提取 RNA，并通过实时 PCR 定量 ADA 基因表达。还评估了 ADA 活性。我们发现，与未治疗组相比，HU 治疗组患者的单核细胞中 ADA 转录本高两倍（P=0.039）。HU 治疗组的单核细胞表达 CD26，而对照组和未治疗组的单核细胞则不表达（P=0.023）。在治疗组中，与未治疗组相比，T 淋巴细胞表达 CD39 的比例降低（P=0.003），且与未治疗组（P=0.017）和对照组（P=0.0009）相比，T 调节（Treg）细胞的比例降低。此外，HU 治疗组的 ADA 活性高于未治疗组。我们的研究结果表明，HU 通过降低腺苷水平及其对 SCA 病理生理过程的影响，发挥出一种新的作用机制。
