ArticleJournal of cellular and molecular medicine2022
Venetoclax enhances DNA damage induced by XPO1 inhibitors: A novel mechanism underlying the synergistic antileukaemic effect in acute myeloid leukaemia.
Article in Journal of cellular and molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- XPO1: From basic research to clinical treatment (Review).Oncology reports · 2026Review
- Venetoclax for elderly patients with acute myeloid leukaemia unfit for intensive chemotherapy: Prospects, resistance mechanisms and management strategies.Clinical and translational medicine · 2026Review
- Targeting the nuclear export receptor exportin-1 in acute myeloid leukaemia: From biology to clinical translation.Clinical and translational medicine · 2026Review
- Selinexor and Venetoclax Combination in Patients With Relapsed or Refractory Acute Myeloid Leukemia.American journal of hematology · 2026Article
- Review
- Innovative evaluation of selinexor and JQ1 synergy in leukemia therapy via C-MYC inhibition.Journal of translational medicine · 2025Article
- Targeting the undruggable MYC in cancer: the rationale of using XPO1 inhibitors.Molecular biology reports · 2025Review
- CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- XPO1/Exportin-1 in Acute Myelogenous Leukemia; Biology and Therapeutic Targeting.Biomolecules · 2025Review
- Targeting ribonucleotide reductase to enhance the antileukemic activity of gilteritinib against chemoresistantASPET discovery · 2025Article
- Disulfidptosis-related lncRNA signature to assess the immune microenvironment and drug sensitivity in acute myeloid leukemia.Scientific reports · 2024Article
- XPO1 inhibition displays anti-leukemia efficacy against DNMT3A-mutant acute myeloid leukemia via downregulating glutathione pathway.Annals of hematology · 2024Article
- Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies.International journal of molecular sciences · 2024Review
- Novel-and Not So Novel-Inhibitors of the Multifunctional CRM1 Protein.Oncology reviews · 2024Review
- Therapeutic targeting of nuclear export and import receptors in cancer and their potential in combination chemotherapy.IUBMB life · 2024Review
- Pharmacological inhibition of MYC to mitigate chemoresistance in preclinical models of squamous cell carcinoma.Theranostics · 2024Article
- Emerging and Future Targeted Therapies for Pediatric Acute Myeloid Leukemia: Targeting the Leukemia Stem Cells.Biomedicines · 2023Review
- Prognostic value and therapeutic targeting of XPO1 in chronic lymphocytic leukemia.Clinical and experimental medicine · 2023Article
- "FLipping" the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors.Cancers · 2022Review
- Venetoclax enhances DNA damage induced by XPO1 inhibitors: A novel mechanism underlying the synergistic antileukaemic effect in acute myeloid leukaemia.Journal of cellular and molecular medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Acute myeloid leukaemia (AML) is a highly heterogeneous haematologic malignancy with poor prognosis. We previously showed synergistic antileukaemic interaction between exportin 1 (XPO1) inhibitor KPT-330 (Selinexor) and Bcl-2 inhibitor venetoclax (ABT-199) in preclinical models of AML, which was partially meditated by Mcl-1, although the full mechanism of action remains unknown. In this study, using real-time RT-PCR and Western blot analysis, we show that inhibition of XPO1 via KPT-330 or KPT-8602 (Eltanexor) decreases the mRNA and protein levels of c-Myc, CHK1, WEE1, RAD51 and RRM2. KPT-330 and KPT-8602 induce DNA damage, as determined by alkaline comet assay. In addition, we demonstrate that venetoclax enhances KPT-330- and KPT-8602-induced DNA damage, likely through inhibition of DNA damage repair. This study provides new insight into the molecular mechanism underlying the synergistic antileukaemic activity between venetoclax and XPO1 inhibitors against AML. Our data support the clinical evaluation of this promising combination therapy for the treatment of AML.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.