Krejcik Zdenek, Kundrat David, Klema Jiri, Hrustincova Andrea, Trsova Iva, Belickova Monika, Cermak Jaroslav, Jonasova Anna, Dostal Jiri, Dostalova Merkerova Michaela
Department of Genomics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
Department of Computer Science, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic.
Biomark Res. 2025 Jan 23;13(1):13. doi: 10.1186/s40364-025-00725-x.
Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source of genome instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors of TEs. However, the roles of TEs and piRNAs in MDS remain unclear.
In this study, we examined TE and piRNA expression through parallel RNA and small RNA sequencing of CD34+ hematopoietic stem cells from MDS patients.
Comparative analysis of TE and piRNA expression between MDS and control samples revealed several significantly dysregulated molecules. However, significant differences were observed between lower-risk MDS (LR-MDS) and higher-risk MDS (HR-MDS) samples. In HR-MDS, we found an inverse correlation between decreased TE levels and increased piRNA expression and these TE and piRNA levels were significantly associated with patient outcomes. Importantly, the upregulation of PIWIL2, which encodes a key factor in the piRNA pathway, independently predicted poor prognosis in MDS patients, underscoring its potential as a valuable disease marker. Furthermore, pathway analysis of RNA sequencing data revealed that dysregulation of the TE‒piRNA axis is linked to the suppression of processes related to energy metabolism, the cell cycle, and the immune response, suggesting that these disruptions significantly affect cellular activity.
Our findings demonstrate the parallel dysregulation of TEs and piRNAs in HR-MDS patients, highlighting their potential role in MDS progression and indicating that the PIWIL2 level is a promising molecular marker for prognosis.
骨髓增生异常肿瘤（MDS）是一类异质性造血系统疾病，其特征为造血无效和基因组不稳定。转座元件（TE）的激活是导致肿瘤发生的基因组不稳定的重要来源，而小的PIWI相互作用RNA（piRNA）作为TE的细胞抑制因子发挥作用。然而，TE和piRNA在MDS中的作用仍不清楚。
在本研究中，我们通过对MDS患者的CD34⁺造血干细胞进行平行RNA和小RNA测序来检测TE和piRNA的表达。
MDS与对照样本之间TE和piRNA表达的比较分析揭示了几种显著失调的分子。然而，在低危MDS（LR-MDS）和高危MDS（HR-MDS）样本之间观察到了显著差异。在HR-MDS中，我们发现TE水平降低与piRNA表达增加呈负相关，并且这些TE和piRNA水平与患者预后显著相关。重要的是，编码piRNA途径关键因子的PIWIL2的上调独立预测MDS患者预后不良，突出了其作为有价值疾病标志物的潜力。此外，RNA测序数据的通路分析表明，TE-piRNA轴的失调与能量代谢、细胞周期和免疫反应相关过程的抑制有关，提示这些干扰显著影响细胞活性。
我们的研究结果表明HR-MDS患者中TE和piRNA存在平行失调，突出了它们在MDS进展中的潜在作用，并表明PIWIL2水平是一个有前景的预后分子标志物。
