ArticleOncoTargets and therapy2019
Suppressing Hedgehog signaling reverses drug resistance of refractory acute myeloid leukemia.
Article in OncoTargets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Efficacy and Safety of Conditioning Regimen with Chidamide Plus TMI/Cy/Flu Followed by Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk and R/R AML.Stem cell reviews and reports · 2025Article
- Review
- Advances in the role of the IGF signaling system in myelodysplastic syndromes and acute myeloid leukemia.Frontiers in oncology · 2025Review
- Myeloperoxidase and Thyrotropin-Releasing Hormone Within Leukaemia Stem Cells Increased Chemosensitivity in Acute Myeloid Leukaemia.Journal of cellular and molecular medicine · 2024Article
- The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways.Cell communication and signaling : CCS · 2023Review
- Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL).International journal of molecular sciences · 2023Review
- Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives.Cancers · 2021Review
- Hedgehog Signaling in Myeloid Malignancies.Cancers · 2021Review
- Understanding the Hedgehog Signaling Pathway in Acute Myeloid Leukemia Stem Cells: A Necessary Step toward a Cure.Biology · 2021Review
- Inhibition of EZH2 by chidamide exerts antileukemia activity and increases chemosensitivity through Smo/Gli-1 pathway in acute myeloid leukemia.Journal of translational medicine · 2021Article
- GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia.Cell death & disease · 2021Article
- The Role of Notch, Hedgehog, and Wnt Signaling Pathways in the Resistance of Tumors to Anticancer Therapies.Frontiers in cell and developmental biology · 2021Review
- Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.Signal transduction and targeted therapy · 2020Review
- Downregulation of GLI3 Expression Mediates Chemotherapy Resistance in Acute Myeloid Leukemia.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHedgehog (Hh) signaling is involved in the pathogenesis of tumors. By performing gene chip analysis, we predicted that Hh signaling might regulate multiple downstream pathways in acute myeloid leukemia (AML).
methodsIn this study, the potential role of the Hh pathway in refractory AML, and the impact of Hh expression on clinical prognosis were examined. We also investigated the role of the Hh inhibitor NVP-LDE225 in reversing drug resistance of refractory primary AML cells in vitro and the roles of multiple drug-resistant HL60/Adriamycin-resistant cells in vitro and in vivo (in a xenograft mouse model). Finally, we explored the underlying mechanisms.
resultsHh pathway was highly active in chemotherapy-resistant AML cells; by contrast, activation was less pronounced in chemosensitive cells and non-refractory primary cells. Strong activation of this pathway was associated with higher recurrence rates and poorer relapse-free and overall survival. NVP-LDE225 inhibited MRP1 protein expression, increased intracellular accumulation of Adriamycin, and reversed chemotherapeutic resistance. These effects were likely mediated through inhibition of the IGF-1R/Akt/MRP1 pathway. In the AML xenograft mouse model, NVP-LDE225 plus Adriamycin resulted in marked tumor regression.
conclusionThese findings suggest that targeting the Hh pathway might be a therapeutic avenue for overcoming MDR resistance and preventing refractory AML.
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