Activating mutations of c-kit at codon 816 confer drug resistance in human leukemia cells

Z. Q. Ning, J. Li, R. J. Arceci

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations


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 languageEnglish (US)
Pages (from-to)513-522
Number of pages10
JournalLeukemia and Lymphoma
Issue number5-6
StatePublished - 2001
Externally publishedYes


  • Apoptosis
  • C-kit
  • Drug Resistance
  • Mutation
  • Proliferation
  • Stem cell factor

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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