Merkerova Michaela Dostalova, Krejcik Zdenek, Belickova Monika, Hrustincova Andrea, Klema Jiri, Stara Eliška, Zemanova Zuzana, Michalova Kyra, Cermak Jaroslav, Jonasova Anna
Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
Department of Cybernetics, Faculty of Electrical Engineering, Czech Technical University, Prague, Czech Republic.
Eur J Haematol. 2015 Jul;95(1):35-43. doi: 10.1111/ejh.12458. Epub 2014 Nov 11.
Lenalidomide is a potent drug with pleiotropic effects in patients with myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 5 [del(5q)]. We investigated its effect on regulation of microRNA (miRNA) expression profiles in del(5q) patients with MDS in vivo.
We used miRNA expression microarrays to study changes in miRNA levels in peripheral blood CD14+ monocytes collected from patients before and during lenalidomide treatment and compared them with those from healthy donors.
Before treatment, we observed strong upregulation of pro-apoptotic miR-34a and miR-34a* that diminished during lenalidomide exposure. Upregulation of HOX-related miR-196b and erythroid-specific miR-451 seen in untreated patients remained unchanged after the treatment. At the time of hematologic response, expression of several miRNAs clustering to the 14q32 locus was reduced. Additionally, we focused more deeply on miRNAs from the 5q commonly deleted region and found that levels of miR-378 and miR-378* followed haploinsufficiency trend.
This report describes changes in miRNA expression in del(5q) patients with MDS treated with lenalidomide, likely arising from deregulation of pathways implicated in lenalidomide action.
来那度胺是一种对伴有5号染色体长臂缺失[del(5q)]的骨髓增生异常综合征（MDS）患者具有多效性作用的强效药物。我们在体内研究了其对del(5q) MDS患者微小RNA（miRNA）表达谱调控的影响。
我们使用miRNA表达微阵列来研究来那度胺治疗前及治疗期间从患者采集的外周血CD14+单核细胞中miRNA水平的变化，并将其与健康供体的进行比较。
治疗前，我们观察到促凋亡miR-34a和miR-34a强烈上调，在来那度胺治疗期间这种上调减弱。未经治疗患者中观察到的HOX相关miR-196b和红系特异性miR-451的上调在治疗后保持不变。在血液学缓解时，聚集在14q32位点的几种miRNA的表达降低。此外，我们更深入地关注了来自5q常见缺失区域的miRNA，发现miR-378和miR-378的水平呈现单倍剂量不足趋势。
本报告描述了用 来那度胺治疗的del(5q) MDS患者中miRNA表达的变化，这可能是由于来那度胺作用相关途径的失调引起的。
