Evaluation of Combined Decitabine and Olaparib Treatment in Acute Promyelocytic Leukemia Cell Line

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Sancak A., R.S Abusalim M., Taheri S., Mehmetbeyoğlu Duman S. E.

11. Multidisipliner Kanser Araştırma Kongresi , İstanbul, Türkiye, 2 - 05 Temmuz 2026, ss.122-123, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: İstanbul
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.122-123
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Erciyes Üniversitesi Adresli: Evet

Özet

Introduction and Aim: Acute promyelocytic leukemia (APL) is a hematological malignancy characterized by differentiation arrest and abnormal promyelocyte proliferation1. Despite therapeutic advances, resistance and relapse remain significant hurdles. Epigenetic dysregulation and impaired DNA damage repair (DDR) pathways are critical drivers of leukemogenesis2. This study investigates the molecular synergy between the hypomethylating agent Decitabine (Dec) and the PARP inhibitor Olaparib (Ola) in the HL-60 model, specifically focusing on the modulation of DDR genes and markers of cellular stress and survival. Olaparib (Ola) in the HL-60 model, specifically focusing on the modulation of DDR genes and markers of cellular stress and survival.

Materials and Methods: HL-60 cells were treated with Dec, Ola, or their combination. The mRNA expression levels of epigenetic regulators and DNA repair-related genes, including DNMT2, TET2, PTEN, RAD51, and EXO1, were quantified by qPCR analysis. In parallel, protein expression levels of γH2A.X, RAD51, and STAT5A were evaluated by Western blotting at 24 and 48 hours to investigate treatment-induced genomic instability, DNA damage response activation, and compensatory survival signaling pathways.

Results: The combination-treatment induced a distinct molecular profile. qPCR revealed that while Dec and Ola individually suppressed PTEN, the combination significantly reactivated its expression. Ola acted as a potent inducer of TET2 and RAD51 transcripts. Immunoblotting confirmed synergistic effects, with combination-treated cells showing sustained H2A.X phosphorylation and significant RAD51 protein upregulation at 48 hours. Additionally, the combination triggered increased STAT5A protein levels, indicating a compensatory survival response to extensive DNA damage.

Discussion: These findings suggest that Dec and Ola combination overwhelms the DNA repair capacity of HL-60 cells, shifting reliance toward RAD51-mediated homologous recombination. The reactivation of the tumor suppressor PTEN underscores the therapeutic potential of this dual-targeting strategy. However, the induction of STAT5A survival signaling highlights a potential resistance mechanism. Overall, combining epigenetic modulation with DDR inhibition represents a promising approach for treating APL.

Keywords: Acute promyelocytic leukemia (APL), PARP, Decitabine