Journal
LEUKEMIA & LYMPHOMA
Volume 63, Issue 3, Pages 729-737Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10428194.2021.1998484
Keywords
Ribonucleotide reductase (RNR); myelodysplastic syndrome; methylation; 5-azacytidine; response to treatment
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Funding
- Genesis Pharma [GE00036/2018]
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The study found that in MDS treatment, RNR expression is correlated with clinical outcomes, with low RRM1 levels associated with RRM1 methylation status affecting patient response to 5-azacytidine treatment. Splicing factor mutations may be related to a decrease in RRM1 mRNA levels.
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 (p = 0.005) and a better response to treatment with 5-azacytidine (p = 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 (p = 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.
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