Significance of PARP1 Expression levels in patients with Acute Myeloid Leukemia

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Leukaemia
Translational Research
Presenter Hossein Pashaiefar
Citation Annals of Oncology (2018) 29 (suppl_9): ix87-ix93. 10.1093/annonc/mdy437
Authors H. Pashaiefar1, M. Yaghmaie2, J. Tavakkoly-Bazzaz3, S.H. Ghaffari1, K. Alimoghaddam4, M. Momeny1, M. Izadifard4, A. Kasaeian1, A. Ghavamzadeh4
  • 1Hematology, Oncology, Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, 1411713135 - Tehran/IR
  • 2Hematology & Oncology, Tehran University Of Medical Science, 1419743141 - Tehran/IR
  • 3Medical Genetics, Tehran University Of Medical Science, 1419743141 - Tehran/IR
  • 4Hematology & Oncology, Hematology, Oncology and Stem cell Transplantation Research Center, Tehran University of Medical Sciences, 1419743141 - Tehran/IR

Abstract

Background

Poly (ADP-ribose) polymerase-1 (PARP1) is a DNA binding protein that has an important function in different forms of DNA repair. Its prognostic value is demonstrated in different types of human cancer. However, PARP1 expression and its prognostic value in acute myeloid leukemia (AML) patients has not yet been fully understood. In this study, we quantified the PARP1 expression levels in AML patients and determined its correlation with clinical characteristics and laboratory findings of AML patients.

Methods

Using quantitative polymerase chain reaction (qPCR) the expression levels of PARP1 were evaluated in 86 AML patients (65 non-M3 and 21 M3 patients) and 54 healthy individuals. The correlation of PARP1 expression with clinicopathological factors of patients was statistically analyzed.

Results

AML patients had elevated levels of PARP1 expression compared with healthy individuals (p < 0.001). Patients with chromosomal translocations trend to have higher expression of PARP1 compared with those without chromosomal translocations (p < 0.001). Among non-M3 AML patients, those with complex chromosomal abnormalities have higher PARP1 expression compared to patients with normal karyotype and single chromosomal abnormalities (p = 0.006). In addition, patients with adverse cytogenetic risk had higher PARP1 expression compared with other cytogenetic risk groups (p = 0.004). Based on median level of PARP1 expression non-M3 AML patients were divided into PARP1 low-expressed and PARP1 high-expressed groups. Survival analysis showed that high PARP1 expressing patients had shorter overall survival (OS) (p = 0.004) and relapse free survival (RFS) (p = 0.003). Multivariate analysis confirmed high PARP1 expression as an independent risk factor.

Conclusions

Our study therefore suggests that PARP1 may have promoting effects on the formation of chromosomal abnormalities in AML patients. Moreover, high PARP1 level may define an important risk factor in Non M3-AML patients and provide potential therapeutic targets for treatment of AML patients.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.