TY - JOUR
TI - Bone marrow ribonucleotide reductase mRNA levels and methylation status
as prognostic factors in patients with myelodysplastic syndrome treated
with 5-Azacytidine
AU - Kontandreopoulou, Christina-Nefeli
AU - Diamantopoulos, Panagiotis T. and
AU - Giannopoulos, Andreas
AU - Symeonidis, Argiris
AU - Kotsianidis, Ioannis
AU - and Pappa, Vasiliki
AU - Galanopoulos, Athanasios
AU - Panayiotidis,
AU - Panayiotis
AU - Dimou, Maria
AU - Solomou, Elena
AU - Loupis, Theodoros and
AU - Zoi, Katerina
AU - Giannakopoulou, Nefeli
AU - Dryllis, Georgios and
AU - Hatzidavid, Sevastianos
AU - Viniou, Nora-Athina
AU - Hellenic MDS Study
AU - Grp
JO - Leukemia & Lymphoma
PY - 2022
VL - 63
TODO - 3
SP - 729-737
PB - ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
SN - 1042-8194, 1029-2403
TODO - 10.1080/10428194.2021.1998484
TODO - Ribonucleotide reductase (RNR); myelodysplastic syndrome; methylation;
5-azacytidine; response to treatment
TODO - 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.
ER -