Bone marrow ribonucleotide reductase mRNA levels and methylation status as prognostic factors in patients with myelodysplastic syndrome treated with 5-Azacytidine.

Autor: Kontandreopoulou CN; Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece., Diamantopoulos PT; Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece., Giannopoulos A; Haematology Research Lab, Clinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation, Athens, Greece., Symeonidis A; Department of Internal Medicine, University Hospital of Patras, Rio, Greece., Kotsianidis I; Department of Hematology, University Hospital of Alexandroupolis, Alexandroupolis, Greece., Pappa V; Haematology Division, Second Department of Internal Medicine, Attikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece., Galanopoulos A; Department of Clinical Hematology, 'G. Gennimatas' District General Hospital, Athens, Greece., Panayiotidis P; First Department of Propedeutic Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece., Dimou M; First Department of Propedeutic Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece., Solomou E; Department of Internal Medicine, University Hospital of Patras, Rio, Greece., Loupis T; Haematology Research Lab, Clinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation, Athens, Greece., Zoi K; Haematology Research Lab, Clinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation, Athens, Greece., Giannakopoulou N; Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece., Dryllis G; Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece., Hatzidavid S; Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece., Viniou NA; Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Jazyk: angličtina
Zdroj: Leukemia & lymphoma [Leuk Lymphoma] 2022 Mar; Vol. 63 (3), pp. 729-737. Date of Electronic Publication: 2021 Nov 05.
DOI: 10.1080/10428194.2021.1998484
Abstrakt: 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.
Databáze: MEDLINE
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