Τίτλος:
Bone marrow PARP1 mRNA levels predict response to treatment with 5-azacytidine in patients with myelodysplastic syndrome
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Poly (ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme that participates in the DNA repair of malignant cells, with various consequences on their survival. We have recently shown that PARP1 mRNA levels in the bone marrow of patients with myelodysplastic syndrome (MDS) are correlated to prognosis. To evaluate PARP1 as a biomarker of response to 5-azacytidine in patients with MDS, we measured PARP1 mRNA levels by a quantitative real-time PCR in diagnostic bone marrow samples of 77 patients with MDS treated with 5-azacytidine. Patients with higher PARP1 mRNA levels had a better response to 5-azacytidine per the IWG criteria (p = 0.006) and a longer median survival after 5-azacytidine initiation (p = 0.033). Multivariate analysis revealed that PARP1 mRNA level was the only factor affecting response to treatment and survival after treatment with 5-azacytidine. A next-generation sequencing for 40 genes of interest in MDS and quantification of the methylation levels of the PARP1 promoter were also carried out in a subset of samples (16 and 18 samples respectively). It is the first time that a single, easily measurable biomarker shows a clear correlation with response to treatment and survival in a patient population consisting of previously untreated patients with MDS homogeneously treated with 5-azacytidine. The fact that PARP1 is also a treatment target in several malignancies underscores the importance of our finding for the potential use of PARP1 inhibitors in MDS. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
Συγγραφείς:
Diamantopoulos, P.T.
Kontandreopoulou, C.-N.
Symeonidis, A.
Kotsianidis, I.
Pappa, V.
Galanopoulos, A.
Vassilakopoulos, T.
Dimou, M.
Solomou, E.
Kyrtsonis, M.-C.
Siakantaris, M.
Angelopoulou, M.
Kourakli, A.
Papageorgiou, S.
Christopoulou, G.
Roumelioti, M.
Panayiotidis, P.
Viniou, N.-A.
On behalf of the Hellenic MDS Study Group
Περιοδικό:
Annals of Hematology
Λέξεις-κλειδιά:
antimetabolite; azacitidine; biological marker; messenger RNA; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; PARP1 protein, human, aged; biosynthesis; bone marrow; chemistry; DNA damage; DNA methylation; DNA repair; drug effect; female; genetics; human; Kaplan Meier method; male; metabolism; middle aged; myelodysplastic syndrome; prognosis; promoter region; proportional hazards model; upregulation; very elderly, Aged; Aged, 80 and over; Antimetabolites; Azacitidine; Biomarkers; Bone Marrow; DNA Damage; DNA Methylation; DNA Repair; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myelodysplastic Syndromes; Poly (ADP-Ribose) Polymerase-1; Prognosis; Promoter Regions, Genetic; Proportional Hazards Models; RNA, Messenger; Up-Regulation
DOI:
10.1007/s00277-019-03650-w
