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Annals of Hematology
Published in: Annals of Hematology 6/2019

01-06-2019 | Myelodysplastic Syndrome | Original Article

Bone marrow PARP1 mRNA levels predict response to treatment with 5-azacytidine in patients with myelodysplastic syndrome

Authors: Panagiotis T. Diamantopoulos, Christina-Nefeli Kontandreopoulou, Argiris Symeonidis, Ioannis Kotsianidis, Vassiliki Pappa, Athanasios Galanopoulos, Theodoros Vassilakopoulos, Maria Dimou, Eleni Solomou, Marie-Christine Kyrtsonis, Marina Siakantaris, Maria Angelopoulou, Alexandra Kourakli, Sotirios Papageorgiou, Georgia Christopoulou, Maria Roumelioti, Panayiotis Panayiotidis, Nora-Athina Viniou, On behalf of the Hellenic MDS Study Group

Published in: Annals of Hematology | Issue 6/2019

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Abstract

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.
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Metadata
Title
Bone marrow PARP1 mRNA levels predict response to treatment with 5-azacytidine in patients with myelodysplastic syndrome
Authors
Panagiotis T. Diamantopoulos
Christina-Nefeli Kontandreopoulou
Argiris Symeonidis
Ioannis Kotsianidis
Vassiliki Pappa
Athanasios Galanopoulos
Theodoros Vassilakopoulos
Maria Dimou
Eleni Solomou
Marie-Christine Kyrtsonis
Marina Siakantaris
Maria Angelopoulou
Alexandra Kourakli
Sotirios Papageorgiou
Georgia Christopoulou
Maria Roumelioti
Panayiotis Panayiotidis
Nora-Athina Viniou
On behalf of the Hellenic MDS Study Group
Publication date
01-06-2019
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 6/2019
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-019-03650-w

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