Expression and activation of SHC/MAP kinase pathway in primary acute myeloid leukemia blasts

P. Lunghi, A. Tabilio, S. Pinelli, G. Valmadre, E. Ridolo, R. Albertini, C. Carlo-Stella, P. P. Dall'Aglio, P. G. Pelicci, A. Bonati

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Abstract

Introduction: We report the results of a study investigating signaling proteins in 26 cases of primary acute myelogenous leukemia. We studied the Shc adaptor proteins p52/p46Shc, which can activate the RAS/Mitogen Activated Protein kinase pathway, p66Shc which is uncoupled from RAS/MAP kinases and the MAP kinase family members Extracellular signal Regulated Kinase (ERK) and c-Jun NH2-terminal protein Kinase (JNK) or Stress Activated Protein Kinase (SAPK). Material and methods: CD34+ and CD34- fractions of four human normal bone marrow and unfractionated bone marrow samples were investigated. Immunoblottings, immunoenzymatic and in vitro assays were performed. Results: Shc protein isoforms were constitutively expressed in all the AML cases examined. Tyrosine-phosphorylation of p53/p46Shc isoforms were found in CD34+ but not in the majority of CD34- cases. p66Shc isoform was not tyrosine-phosphorylated in CD34-, and was tyrosine-phosphorylated only in some CD34+ cases. Expression and activation of ERK was constitutively present in the majority of AML patients analysed. JNK/SAPK was expressed but not activated in the AMLs examined. Activation occurred after treatment of the leukemic cells by anisomycin, etoposide, and cytarabine. ERK and JNK/SAPK activation were not detectable in the hematopoietic precursors of human normal bone-marrow. Conclusion: These data bear implications for the role of Shc-MAP kinase pathway in normal hemopoiesis and AML leukemogenesis.

Original languageEnglish
Pages (from-to)70-80
Number of pages11
JournalHematology Journal
Volume2
Issue number2
DOIs
Publication statusPublished - 2001

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Keywords

  • Acute myeloid leukemia
  • ERK kinases
  • JNK/SAPK kinases
  • Shc adaptor proteins
  • Signal transduction

ASJC Scopus subject areas

  • Hematology

Cite this

Lunghi, P., Tabilio, A., Pinelli, S., Valmadre, G., Ridolo, E., Albertini, R., Carlo-Stella, C., Dall'Aglio, P. P., Pelicci, P. G., & Bonati, A. (2001). Expression and activation of SHC/MAP kinase pathway in primary acute myeloid leukemia blasts. Hematology Journal, 2(2), 70-80. https://doi.org/10.1038/sj.thj.6200095