Livun Ana, Newberry Kate J, Manshouri Taghi, Kusec Rajko, Verstovsek Srdan
Division of Molecular Diagnostics and Genetics, Department of Laboratory Diagnosis, Dubrava University Hospital, Zagreb, Croatia.
Department of Leukemia, The University of MD Anderson Cancer Center, Houston, TX, U.S.A.
Anticancer Res. 2015 Oct;35(10):5219-23.
The purpose of the present study was to determine whether genes involved in the organization of the hematopoietic niche were dysregulated in patients with primary myelofibrosis (MF) treated with lenalidomide.
We used reverse-transcription quantitative polymerase chain reaction to study the expression of a set of genes involved in the organization of the hematopoietic niche in peripheral blood and bone marrow (BM) mononuclear cell (MNC) samples from 32 patients with primary MF who participated in a phase II trial of lenalidomide plus prednisone.
At baseline (before treatment) cyclo-oxygenase 2 (COX2) was significantly up-regulated, while chemokine (C-X-C motif) receptor 4 (CXCR4), paired box 5 (PAX5) C-terminus, and hypoxia inducible factor 1A (HIF1A) were significantly down-regulated in BM MNCs from patients with primary MF compared to BM MNCs from healthy individuals. After 9 months of treatment, the expression of suppressor of cytokine signaling 3 (SOCS3) was significantly increased.
Patients with primary MF showed aberrant expression of several genes involved in maintaining BM homeostasis and our findings suggest that treatment with lenalidomide plus prednisone up-regulates SOCS3.
本研究旨在确定来那度胺治疗的原发性骨髓纤维化（MF）患者中，参与造血微环境组织的基因是否失调。
我们使用逆转录定量聚合酶链反应，研究了参与造血微环境组织的一组基因在32例参与来那度胺加泼尼松II期试验的原发性MF患者的外周血和骨髓（BM）单个核细胞（MNC）样本中的表达。
在基线（治疗前）时，与健康个体的BM MNC相比，原发性MF患者的BM MNC中环氧合酶2（COX2）显著上调，而趋化因子（C-X-C基序）受体4（CXCR4）、配对盒5（PAX5）C端和缺氧诱导因子1A（HIF1A）显著下调。治疗9个月后，细胞因子信号转导抑制因子3（SOCS3）的表达显著增加。
原发性MF患者表现出参与维持BM稳态的几个基因的异常表达，我们的研究结果表明来那度胺加泼尼松治疗可上调SOCS3。
