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Updated: Jun 9, 2026
Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
Hedgehog signaling maintains chemoresistance in myeloid leukemic cells
K C S Queiroz1, R R Ruela-de-Sousa, G M Fuhler
1Department of Biochemistry, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil. k.c.desouzaqueiroz@amc.uva.nl
Abstract:
The development of resistance against chemotherapy remains one of the major challenges in the clinical management of leukemia. There is still limited insight into the molecular mechanisms that maintain the chemotherapy-resistant phenotype, despite the obvious clinical relevance that such knowledge would have. In this study, we show that the chemotherapy-resistant phenotype of myeloid leukemia cells correlates with activation of the Hedgehog (Hh) pathway, whereas in chemosensitive cells, such activation is less pronounced. Importantly, the overexpression of Hh pathway components induces chemoprotection and inhibition of the pathway reverts chemoresistance of Lucena-1 cells, apparently by interfering with P-glycoprotein-dependent drug resistance. Our data thus identify the Hh pathway as an essential component of multidrug resistance (MDR) myeloid leukemia and suggest that targeting the Hh pathway might be an interesting therapeutic avenue for overcoming MDR resistance in myeloid leukemia.
Insights
Chemotherapy resistance in myeloid leukemia is linked to the Hedgehog (Hh) pathway. Inhibiting this pathway can reverse drug resistance, offering a potential new treatment strategy for leukemia.
Area of Science:
- Oncology
- Molecular Biology
- Hematology
Background:
- Chemotherapy resistance is a significant clinical challenge in leukemia treatment.
- The molecular mechanisms underlying chemotherapy resistance are not fully understood.
Purpose of the Study:
- To investigate the role of the Hedgehog (Hh) pathway in chemotherapy resistance in myeloid leukemia.
- To explore the potential of targeting the Hh pathway for overcoming drug resistance.
Main Methods:
- Correlation analysis of Hh pathway activation in chemotherapy-resistant versus sensitive myeloid leukemia cells.
- Experimental manipulation of Hh pathway components to assess effects on chemoprotection and chemoresistance.
- Investigation of P-glycoprotein's role in Hh pathway-mediated drug resistance.
Main Results:
- Chemotherapy-resistant myeloid leukemia cells exhibit higher activation of the Hedgehog (Hh) pathway compared to chemosensitive cells.
- Overexpression of Hh pathway components confers chemoprotection.
- Inhibition of the Hh pathway reverses chemoresistance in Lucena-1 cells, potentially by affecting P-glycoprotein-dependent drug resistance.
Conclusions:
- The Hedgehog (Hh) pathway is a key component of multidrug resistance (MDR) in myeloid leukemia.
- Targeting the Hh pathway presents a promising therapeutic strategy to overcome MDR in myeloid leukemia.
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