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