POLY [ADP-RIBOSE] POLYMERASE 1 (PARP-1) EXPRESSION IS CORRELATED TO THE TYPE OF MYELODYSPLASTIC SYNDROME ACCORDING TO BOTH WHO CLASSIFICATION AND IPSS SCORE
(Abstract release date: 05/19/16)
EHA Library. Diamantopoulos P. 06/09/16; 132757; E1208
Dr. Panagiotis Diamantopoulos
Contributions
Contributions
Abstract
Abstract: E1208
Type: Eposter Presentation
Background
Poly [ADP-ribose] polymerase 1 (PARP-1) has a central role in the repair of single-stranded DNA breaks, thus protecting the cell from genomic instability. Overexpression of PARP1 may lead a cell to apoptotic or necrotic death, thus defining the cell’s fate. Genetic defects are important in the pathogenesis of myelodysplastic syndromes (MDS) and the role of PARP1 in the apoptotic pathways seems to be promising, since new agents targeting PARP1 are available. PARP1 expression has never been studied in MDS.
Aims
Our aim was to detect PARP1 mRNA in bone marrow samples of patients with MDS and investigate its correlations to the hematologic and prognostic characteristics of the patients.
Methods
Bone marrow samples were collected from patients with MDS. Quantification of PARP1 mRNA was performed by a SYBR-green based PCR, performed on BIORADCFX96 (BIORAD) and the results were expressed in correlation to those of the housekeeping gene of beta actin. Statistical correlations were carried out using IBM SPSS statistics, version 19.0.
Results
Fifty three (53) patients with MDS were included in the study. The basic demographic and hematologic characteristics of the patients are shown in the Table. The vast majority of the patients (92.5%) were treatment naïve. The median PARP1 mRNA levels were 0.0259 (range 0.0003 – 0.6410) and showed a statistically significant correlation to the type of MDS ( according to the WHO classification) (p=0.016) and to the IPSS score (p=0.001) (detailed results in Table). The lowest levels were observed in patients with RA (0.0053 vs 0.1477 for non-RA patients, p= 0.016), as well as in patients with low and intermediate 1 IPSS score (0.0107 vs 0.1831, p=0.01) that had almost 20 times lower PARP1 mRNA levels than patients with intermediate 2 and high risk MDS.Table. Patients’ characteristics and results
* hypomethylating agent† Independent Samples Kruskal-Wallis Test, 2-sided p‡ based on only 2 samples
Conclusion
The correlation of higher levels of PARP1 mRNA with higher risk MDS has never been reported in the past. This correlation, if confirmed by larger studies, may render PARP1 a prognostic factor for patients with MDS. Moreover, this result can lay the basis for the design of clinical trials evaluating the use of PARP1 inhibitors in patients with higher risk MDS.
Session topic: E-poster
Keyword(s): MDS
Type: Eposter Presentation
Background
Poly [ADP-ribose] polymerase 1 (PARP-1) has a central role in the repair of single-stranded DNA breaks, thus protecting the cell from genomic instability. Overexpression of PARP1 may lead a cell to apoptotic or necrotic death, thus defining the cell’s fate. Genetic defects are important in the pathogenesis of myelodysplastic syndromes (MDS) and the role of PARP1 in the apoptotic pathways seems to be promising, since new agents targeting PARP1 are available. PARP1 expression has never been studied in MDS.
Aims
Our aim was to detect PARP1 mRNA in bone marrow samples of patients with MDS and investigate its correlations to the hematologic and prognostic characteristics of the patients.
Methods
Bone marrow samples were collected from patients with MDS. Quantification of PARP1 mRNA was performed by a SYBR-green based PCR, performed on BIORADCFX96 (BIORAD) and the results were expressed in correlation to those of the housekeeping gene of beta actin. Statistical correlations were carried out using IBM SPSS statistics, version 19.0.
Results
Fifty three (53) patients with MDS were included in the study. The basic demographic and hematologic characteristics of the patients are shown in the Table. The vast majority of the patients (92.5%) were treatment naïve. The median PARP1 mRNA levels were 0.0259 (range 0.0003 – 0.6410) and showed a statistically significant correlation to the type of MDS ( according to the WHO classification) (p=0.016) and to the IPSS score (p=0.001) (detailed results in Table). The lowest levels were observed in patients with RA (0.0053 vs 0.1477 for non-RA patients, p= 0.016), as well as in patients with low and intermediate 1 IPSS score (0.0107 vs 0.1831, p=0.01) that had almost 20 times lower PARP1 mRNA levels than patients with intermediate 2 and high risk MDS.Table. Patients’ characteristics and results
| Characteristic | Result | ||
| Number of patients, N (%) | 53 (100) | ||
| Sex (Male to female ratio) | 1.41 | ||
| Age (years), median (range) | 76 (45 – 91) | ||
| Previous treatment, N (%)* | 4 (7.5) | PARP1 mRNA, median (range) | p† |
| MDS type (WHO classification), N (%)RARARSRCMDRAEB-1RAEB-2 | 14 (23.0)2 (3.3)11 (18.0)17 (27.9)9 (14.8) | 0.0053 (0.0010-0.5250)0.1546 (0.0003-0.3089) ‡0.0167 (0.0007-0.2226)0.2097 (0.0047-0.6410)0.1477 (0.0060-0.5901) | 0.016 |
| IPSS, N (%)LowIntermediate 1Intermediate 2High | 20 (32.8)16 (26.2)11 (18.0)6 (9.8) | 0.0062 (0.0007-0.5250)0.1639 (0.0003-0.6410)0.2097 (0.0061-0.3184)0.0910 (0.0135-0.5901) | 0.001 |
| Previous treatment, N (%)* | 4 (7.5) | ||
Conclusion
The correlation of higher levels of PARP1 mRNA with higher risk MDS has never been reported in the past. This correlation, if confirmed by larger studies, may render PARP1 a prognostic factor for patients with MDS. Moreover, this result can lay the basis for the design of clinical trials evaluating the use of PARP1 inhibitors in patients with higher risk MDS.
Session topic: E-poster
Keyword(s): MDS
Abstract: E1208
Type: Eposter Presentation
Background
Poly [ADP-ribose] polymerase 1 (PARP-1) has a central role in the repair of single-stranded DNA breaks, thus protecting the cell from genomic instability. Overexpression of PARP1 may lead a cell to apoptotic or necrotic death, thus defining the cell’s fate. Genetic defects are important in the pathogenesis of myelodysplastic syndromes (MDS) and the role of PARP1 in the apoptotic pathways seems to be promising, since new agents targeting PARP1 are available. PARP1 expression has never been studied in MDS.
Aims
Our aim was to detect PARP1 mRNA in bone marrow samples of patients with MDS and investigate its correlations to the hematologic and prognostic characteristics of the patients.
Methods
Bone marrow samples were collected from patients with MDS. Quantification of PARP1 mRNA was performed by a SYBR-green based PCR, performed on BIORADCFX96 (BIORAD) and the results were expressed in correlation to those of the housekeeping gene of beta actin. Statistical correlations were carried out using IBM SPSS statistics, version 19.0.
Results
Fifty three (53) patients with MDS were included in the study. The basic demographic and hematologic characteristics of the patients are shown in the Table. The vast majority of the patients (92.5%) were treatment naïve. The median PARP1 mRNA levels were 0.0259 (range 0.0003 – 0.6410) and showed a statistically significant correlation to the type of MDS ( according to the WHO classification) (p=0.016) and to the IPSS score (p=0.001) (detailed results in Table). The lowest levels were observed in patients with RA (0.0053 vs 0.1477 for non-RA patients, p= 0.016), as well as in patients with low and intermediate 1 IPSS score (0.0107 vs 0.1831, p=0.01) that had almost 20 times lower PARP1 mRNA levels than patients with intermediate 2 and high risk MDS.Table. Patients’ characteristics and results
* hypomethylating agent† Independent Samples Kruskal-Wallis Test, 2-sided p‡ based on only 2 samples
Conclusion
The correlation of higher levels of PARP1 mRNA with higher risk MDS has never been reported in the past. This correlation, if confirmed by larger studies, may render PARP1 a prognostic factor for patients with MDS. Moreover, this result can lay the basis for the design of clinical trials evaluating the use of PARP1 inhibitors in patients with higher risk MDS.
Session topic: E-poster
Keyword(s): MDS
Type: Eposter Presentation
Background
Poly [ADP-ribose] polymerase 1 (PARP-1) has a central role in the repair of single-stranded DNA breaks, thus protecting the cell from genomic instability. Overexpression of PARP1 may lead a cell to apoptotic or necrotic death, thus defining the cell’s fate. Genetic defects are important in the pathogenesis of myelodysplastic syndromes (MDS) and the role of PARP1 in the apoptotic pathways seems to be promising, since new agents targeting PARP1 are available. PARP1 expression has never been studied in MDS.
Aims
Our aim was to detect PARP1 mRNA in bone marrow samples of patients with MDS and investigate its correlations to the hematologic and prognostic characteristics of the patients.
Methods
Bone marrow samples were collected from patients with MDS. Quantification of PARP1 mRNA was performed by a SYBR-green based PCR, performed on BIORADCFX96 (BIORAD) and the results were expressed in correlation to those of the housekeeping gene of beta actin. Statistical correlations were carried out using IBM SPSS statistics, version 19.0.
Results
Fifty three (53) patients with MDS were included in the study. The basic demographic and hematologic characteristics of the patients are shown in the Table. The vast majority of the patients (92.5%) were treatment naïve. The median PARP1 mRNA levels were 0.0259 (range 0.0003 – 0.6410) and showed a statistically significant correlation to the type of MDS ( according to the WHO classification) (p=0.016) and to the IPSS score (p=0.001) (detailed results in Table). The lowest levels were observed in patients with RA (0.0053 vs 0.1477 for non-RA patients, p= 0.016), as well as in patients with low and intermediate 1 IPSS score (0.0107 vs 0.1831, p=0.01) that had almost 20 times lower PARP1 mRNA levels than patients with intermediate 2 and high risk MDS.Table. Patients’ characteristics and results
| Characteristic | Result | ||
| Number of patients, N (%) | 53 (100) | ||
| Sex (Male to female ratio) | 1.41 | ||
| Age (years), median (range) | 76 (45 – 91) | ||
| Previous treatment, N (%)* | 4 (7.5) | PARP1 mRNA, median (range) | p† |
| MDS type (WHO classification), N (%)RARARSRCMDRAEB-1RAEB-2 | 14 (23.0)2 (3.3)11 (18.0)17 (27.9)9 (14.8) | 0.0053 (0.0010-0.5250)0.1546 (0.0003-0.3089) ‡0.0167 (0.0007-0.2226)0.2097 (0.0047-0.6410)0.1477 (0.0060-0.5901) | 0.016 |
| IPSS, N (%)LowIntermediate 1Intermediate 2High | 20 (32.8)16 (26.2)11 (18.0)6 (9.8) | 0.0062 (0.0007-0.5250)0.1639 (0.0003-0.6410)0.2097 (0.0061-0.3184)0.0910 (0.0135-0.5901) | 0.001 |
| Previous treatment, N (%)* | 4 (7.5) | ||
Conclusion
The correlation of higher levels of PARP1 mRNA with higher risk MDS has never been reported in the past. This correlation, if confirmed by larger studies, may render PARP1 a prognostic factor for patients with MDS. Moreover, this result can lay the basis for the design of clinical trials evaluating the use of PARP1 inhibitors in patients with higher risk MDS.
Session topic: E-poster
Keyword(s): MDS
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