Abstract
An improved understanding of how leukemia cells grow and become resistant to treatment remains critical for developing more effective therapies. We have identified activating mutations of c-kit at codon 816 (Asp816) from a revertant of the cytokine-dependent acute myeloid leukemia (AML) cell line, MO7e (D816H), and de novo childhood AML (D816N). Following transduction of the mutant c-kit cDNAs, MO7e cells acquire a growth advantage and resistance to apoptosis in response to chemotherapeutic drugs and ionizing radiation, in addition to cytokine-independent survival. Although stimulation of mutant c-kit-bearing MO7e cells with stem cell factor (SCF), a ligand for c-Kit, does not have a significant effect on cell proliferation, SCF further inhibits apoptosis induced by cytotoxic agents. These results suggest a potentially important role of Asp816 mutations of c-kit in both malignant cell proliferation and resistance to therapy.
Original language | English (US) |
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Pages (from-to) | 513-522 |
Number of pages | 10 |
Journal | Leukemia and Lymphoma |
Volume | 41 |
Issue number | 5-6 |
DOIs | |
State | Published - 2001 |
Externally published | Yes |
Keywords
- Apoptosis
- C-kit
- Drug Resistance
- Mutation
- Proliferation
- Stem cell factor
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research