Resistance Mechanism in FLT3-Expressing Cells
Author Information
Author(s): Ellen Weisberg, Arghya Ray, Erik Nelson, Sophia Adamia, Rosemary Barrett, Martin Sattler, Chengsheng Zhang, John F. Daley, David Frank, Edward Fox, James D. Griffin
Primary Institution: Dana Farber Cancer Institute, Boston, Massachusetts, United States of America
Hypothesis
What are the molecular mechanisms of clinical resistance to FLT3 inhibitors in acute myeloid leukemia?
Conclusion
MOLM13 cells developed cross-resistance to FLT3 inhibitors, associated with increased FLT3 expression and prolonged protein half-life.
Supporting Evidence
- MOLM13 cells showed cross-resistance to both midostaurin and HG-7-85-01.
- Resistance was linked to increased FLT3 protein levels and prolonged half-life.
- Withdrawal of inhibitors could reverse the drug-resistant phenotype.
Takeaway
Researchers found that certain leukemia cells can become resistant to drugs that target a specific protein, making it harder to treat the disease. When the drugs are stopped, the cells can sometimes regain their sensitivity.
Methodology
MOLM13 AML cell lines were made resistant to FLT3 inhibitors through prolonged exposure, and various assays were conducted to assess cell proliferation and protein expression.
Limitations
The study primarily used cell lines, which may not fully replicate the complexity of human disease.
Digital Object Identifier (DOI)
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