Kontandreopoulou Christina-Nefeli, Diamantopoulos Panagiotis T, Giannopoulos Andreas, Symeonidis Argiris, Kotsianidis Ioannis, Pappa Vasiliki, Galanopoulos Athanasios, Panayiotidis Panayiotis, Dimou Maria, Solomou Elena, Loupis Theodoros, Zoi Katerina, Giannakopoulou Nefeli, Dryllis Georgios, Hatzidavid Sevastianos, Viniou Nora-Athina
Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Haematology Research Lab, Clinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation, Athens, Greece.
Leuk Lymphoma. 2022 Mar;63(3):729-737. doi: 10.1080/10428194.2021.1998484. Epub 2021 Nov 5.
Ribonucleotide Reductase (RNR) is a two-subunit (RRM1, RRM2) enzyme, responsible for the conversion of ribonucleotides to deoxyribonucleotides required for DNA replication. To evaluate RNR as a biomarker of response to 5-azacytidine, we measured RNR mRNA levels by a quantitative real-time PCR in bone marrow samples of 98 patients with myelodysplastic syndrome (MDS) treated with 5-azacytidine with parallel quantification of the gene promoter's methylation. Patients with low RRM1 levels had a high RRM1 methylation status ( = 0.005) and a better response to treatment with 5-azacytidine ( = 0.019). A next-generation sequencing for genes of interest in MDS was also carried out in a subset of 61 samples. Splicing factor mutations were correlated with lower RRM1 mRNA levels ( = 0.044). Our results suggest that the expression of RNR is correlated with clinical outcomes, thus its expression could be used as a prognostic factor for response to 5-azacytidine and a possible therapeutic target in MDS.
核糖核苷酸还原酶（RNR）是一种由两个亚基（RRM1、RRM2）组成的酶，负责将核糖核苷酸转化为DNA复制所需的脱氧核糖核苷酸。为了评估RNR作为对5-氮杂胞苷反应的生物标志物，我们通过定量实时PCR测量了98例接受5-氮杂胞苷治疗的骨髓增生异常综合征（MDS）患者骨髓样本中RNR mRNA水平，并同时对基因启动子的甲基化进行了定量。RRM1水平低的患者具有较高的RRM1甲基化状态（P = 0.005），并且对5-氮杂胞苷治疗的反应更好（P = 0.019）。还对61个样本的子集进行了MDS相关基因的二代测序。剪接因子突变与较低的RRM1 mRNA水平相关（P = 0.044）。我们的结果表明，RNR的表达与临床结果相关，因此其表达可作为对5-氮杂胞苷反应的预后因素以及MDS中可能的治疗靶点。
