title: Poly (ADP-ribose) polymerase 1 mRNA levels strongly correlate with the prognosis of myelodysplastic syndromes.
abstract: Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classification, P=0.005) and to the IPSS score (P=0.002). A correlation was also found with the IPSS-R score (P=0.011) and the cytogenetic risk (P=0.008). In all cases, higher PARP1 levels were correlated with a higher risk category. Moreover, we found a significant survival disadvantage for patients with high PARP1 levels (median survival of 37.4 months versus 'not reached' for low PARP1 levels, P=0.0001, and a 5-year survival rate of 29.8 versus 88.9%, respectively). PARP1 mRNA levels were found to be the stronger predictor of survival in multivariate analysis. These correlations have never been reported in the past and may render PARP1 a prognostic factor to be incorporated in the current prognostic systems for MDS, also laying the basis for clinical trials evaluating PARP1 inhibitors in higher-risk MDS.
authors.affiliation: Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Diamantopoulos
authors.affiliation: Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Zervakis
authors.affiliation: Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Zervakis
authors.affiliation: Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Sofotasiou
authors.affiliation: Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: T
authors.initials: T
authors.lastname: Vassilakopoulos
authors.affiliation: Department of Hematology, University Hospital of Alexandroupolis, Alexandroupoli , Greece.
authors.forename: I
authors.initials: I
authors.lastname: Kotsianidis
authors.affiliation: Department of Internal Medicine, University Hospital of Patras, Rio, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Symeonidis
authors.affiliation: Haematology Division, Second Department of Internal Medicine, Attikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Pappa
authors.affiliation: Department of Clinical Hematology, 'G. Gennimatas' District General Hospital, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Galanopoulos
authors.affiliation: Department of Internal Medicine, University Hospital of Patras, Rio, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Solomou
authors.affiliation: Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Kodandreopoulou
authors.affiliation: Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Papadopoulou
authors.affiliation: Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Korkolopoulou
authors.affiliation: Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Mantzourani
authors.affiliation: Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Kyriakakis
authors.affiliation: Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: N-A
authors.initials: NA
authors.lastname: Viniou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D000071137:Poly (ADP-Ribose) Polymerase-1