ArticleEBioMedicine2018
High PARP-1 expression predicts poor survival in acute myeloid leukemia and PARP-1 inhibitor and SAHA-bendamustine hybrid inhibitor combination treatment synergistically enhances anti-tumor effects.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- Diversity and Multi-Target Potential of Pyrazole, Imidazole or Triazole Derivatives in Modern Anticancer Therapy.International journal of molecular sciences · 2026Review
- Selective small molecule targeting of KDM4 as a therapeutic strategy to reduce proliferation of acute myeloid leukaemia.British journal of haematology · 2026Article
- Article
- Exploring the role of PARP1 inhibition in enhancing antibody-drug conjugate therapy for acute leukemias: insights from DNA damage response pathway interactions.Journal of translational medicine · 2024Article
- NL101 synergizes with the BCL-2 inhibitor venetoclax through PI3K-dependent suppression of c-Myc in acute myeloid leukaemia.Journal of translational medicine · 2024Article
- Genetic and Epigenetic Biomarkers Associated with Early Relapse in Pediatric Acute Lymphoblastic Leukemia: A Focused Bioinformatics Study on DNA-Repair Genes.Biomedicines · 2024Article
- Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions.British journal of cancer · 2024Article
- High expression of BCAT1 sensitizes AML cells to PARP inhibitor by suppressing DNA damage response.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Therapeutic targeting of PARP with immunotherapy in acute myeloid leukemia.Frontiers in pharmacology · 2024Review
- Roles ofClinical Medicine Insights. Oncology · 2024Article
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- KLF5 Promotes Tumor Progression and Parp Inhibitor Resistance in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Overexpression of XRCC1 is Associated with Poor Survival in Patients with Head and Neck Squamous Carcinoma and Has Potential to Be Used as Targeted Therapy by Synthetic Lethality.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- PARP-1 improves leukemia outcomes by inducing parthanatos during chemotherapy.Cell reports. Medicine · 2023Article
- PARP-1 Expression Influences Cancer Stem Cell Phenotype in Colorectal Cancer Depending on p53.International journal of molecular sciences · 2023Article
- Review
- Synthesis of New Bioactive Indolyl-1,2,4-Triazole Hybrids As Dual Inhibitors for EGFR/PARP-1 Targeting Breast and Liver Cancer Cells.ACS omega · 2022Article
- DNA Methylation Malleability and Dysregulation in Cancer Progression: Understanding the Role of PARP1.Biomolecules · 2022Review
- Two experts and a newbie: [European journal of nuclear medicine and molecular imaging · 2022Article
- PARP-1 inhibitors enhance the chemosensitivity of leukemia cells by attenuating NF-кB pathway activity and DNA damage response induced by IdarubicinActa biochimica et biophysica Sinica · 2022Article
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPARP-1 plays a critical role in DNA damage repair and contributes to progression of cancer. To explore the role of PARP-1 in acute myeloid leukemia (AML), we analyzed the expression of PARP-1 in AML and its relation to the clinical prognosis. Then, we investigated the efficacy and mechanism of PARP inhibitor BMN673 (Talazoparib) combined with NL101, a novel SAHA-bendamustine hybrid in vitro and in vivo.
methodsThe expression of PARP-1 in 339 cytogenetically normal AML (CN-AML) cases was evaluated using RT-PCR. According to the expression of PARP-1, the clinical characteristics and prognosis of the patients were grouped and compared. The combination effects of BMN673 and NL101 were studied in AML cells and B-NSG mice xenograft model of MV4-11.
findingsWe found patients in high PARP-1 expression group had higher levels of blast cells in bone marrow (P = .003) and white blood cells (WBC) in peripheral blood (P = .008), and were associated with a more frequent FLT3-ITD mutation (28.2% vs 17.3%, P = .031). The overall survival (OS) and event free survival (EFS) of the high expression group were significantly shorter than those in the low expression group (OS, P = .005 and EFS, P = .004). BMN673 combined with NL101 had a strong synergistic effect in treating AML. The combination significantly induced cell apoptosis and arrested cell cycle in G2/M phase. Mechanistically, BMN673 and NL101 combinatorial treatment promoted DNA damage. In vivo, the combination effectively delayed the development of AML and prolonged survival.
interpretationHigh PARP-1 expression predicts poor survival in CN-AML patients. The synergistic effects of PARP inhibitor BMN673 in combination with SAHA-bendamustine hybrid, NL101, provide a new therapeutic strategy against AML. FUND: National Natural Science Foundation of China and Zhejiang Provincial Key Innovation Team.
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