title: Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia.
abstract: Mutations and chromosomal translocations occur in leukemic cells that result in elevated expression or constitutive activation of various growth factor receptors and downstream kinases. The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are often activated by mutations in upstream genes. The Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways are regulated by upstream Ras that is frequently mutated in human cancer. Recently, it has been observed that the FLT-3 and Jak kinases and the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) phosphatase are also frequently mutated or their expression is altered in certain hematopoietic neoplasms. Many of the events elicited by the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways have direct effects on survival pathways. Aberrant regulation of the survival pathways can contribute to uncontrolled cell growth and lead to leukemia. In this review, we describe the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT signaling cascades and summarize recent data regarding the regulation and mutation status of these pathways and their involvement in leukemia.
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Steelman
authors.forename: S L
authors.initials: SL
authors.lastname: Abrams
authors.forename: J
authors.initials: J
authors.lastname: Whelan
authors.forename: F E
authors.initials: FE
authors.lastname: Bertrand
authors.forename: D E
authors.initials: DE
authors.lastname: Ludwig
authors.forename: J
authors.initials: J
authors.lastname: Bäsecke
authors.forename: M
authors.initials: M
authors.lastname: Libra
authors.forename: F
authors.initials: F
authors.lastname: Stivala
authors.forename: M
authors.initials: M
authors.lastname: Milella
authors.forename: A
authors.initials: A
authors.lastname: Tafuri
authors.forename: P
authors.initials: P
authors.lastname: Lunghi
authors.forename: A
authors.initials: A
authors.lastname: Bonati
authors.forename: A M
authors.initials: AM
authors.lastname: Martelli
authors.forename: J A
authors.initials: JA
authors.lastname: McCubrey
mesh_terms: D006801:Humans; D007938:Leukemia / Q000209:etiology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D050791:STAT Transcription Factors; D011494:Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human