Περίληψη:
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.
Συγγραφείς:
Kontandreopoulou, Christina-Nefeli
Diamantopoulos, Panagiotis T. and
Giannopoulos, Andreas
Symeonidis, Argiris
Kotsianidis, Ioannis
and Pappa, Vasiliki
Galanopoulos, Athanasios
Panayiotidis,
Panayiotis
Dimou, Maria
Solomou, Elena
Loupis, Theodoros and
Zoi, Katerina
Giannakopoulou, Nefeli
Dryllis, Georgios and
Hatzidavid, Sevastianos
Viniou, Nora-Athina
Hellenic MDS Study
Grp
