Lack of constitutive activation of MAP kinase pathway in human acute myeloid leukemia cells with N-Ras mutation

M. Iida, M. Towatari, A. Nakao, H. Iida, H. Kiyoi, Y. Nakano, M. Tanimoto, H. Saito, T. Naoe

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


Mitogen-activated protein (MAP) kinases act as transducers of extracellular signaling via tyrosine kinase-growth factor receptors and G-protein-linked receptors to transcription factors. Constitutive activation of MAP kinase has been observed in a variety of solid tumors including renal cancer and breast cancer. Recently, we have reported that constitutively activated MAP kinase was observed in 50% of human primary acute myeloid leukemia (AML) cells. Ras is one of the components of G-proteins and transduces the signal from cytokine receptors to raf-1 theoretically resulting in the activation of MAP kinase pathway. In the present study, we have examined the correlation of Ras mutations and the activation of MAP kinase pathway in patients with AML. Twenty out of 22 AML cases with activating N-Ras mutations showed no phosphorylated forms of ERK2. ERK2 phosphorylation was tightly correlated with ERK1 phosphorylation and MAP kinase activity detected by in vitro kinase assay. Three samples with N-Ras mutations were stimulated with IL-3, GM-CSF and G-CSF separately but ERK2 activation was induced in none of these samples stimulated with these cytokines. In contrast, ERK2 was constitutively activated in all of four pancreatic carcinoma cases with K-Ras mutation at codon 12. These results suggest that function of the Ras mutations may be different between solid tumors, such as pancreatic carcinoma and colorectal carcinoma, and AML. Mutated Ras does not always stimulate MAP kinase pathway constitutively and may rather inhibit classical MAP kinase cascade in AML blasts from leukemia patients.

Original languageEnglish
Pages (from-to)585-589
Number of pages5
Issue number4
Publication statusPublished - 1999


  • AML
  • MAP kinase
  • Mutation
  • Ras

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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