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 journalArticle

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 languageEnglish (US)
Pages (from-to)513-522
Number of pages10
JournalLeukemia and Lymphoma
Volume41
Issue number5-6
StatePublished - 2001

Fingerprint

Stem Cell Factor
Drug Resistance
Codon
Leukemia
Acute Myeloid Leukemia
Mutation
Cell Proliferation
Apoptosis
Cytokines
Cytotoxins
Myeloid Cells
Ionizing Radiation
Complementary DNA
Cell Line
Survival
Therapeutics
Growth
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Activating mutations of c-kit at codon 816 confer drug resistance in human leukemia cells. / Ning, Z. Q.; Li, J.; Arceci, R. J.

In: Leukemia and Lymphoma, Vol. 41, No. 5-6, 2001, p. 513-522.

Research output: Contribution to journalArticle

Ning, Z. Q. ; Li, J. ; Arceci, R. J. / Activating mutations of c-kit at codon 816 confer drug resistance in human leukemia cells. In: Leukemia and Lymphoma. 2001 ; Vol. 41, No. 5-6. pp. 513-522.
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