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 language | English |
---|---|
Pages (from-to) | 70-80 |
Number of pages | 11 |
Journal | Hematology Journal |
Volume | 2 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2001 |
Keywords
- Acute myeloid leukemia
- ERK kinases
- JNK/SAPK kinases
- Shc adaptor proteins
- Signal transduction
ASJC Scopus subject areas
- Hematology