Contributions of the Raf MEK ERK, PI3K PTEN Akt mTOR and Jak STAT pathways to leukemia

• Published in: Leukemia Vol. 22; no. 4; pp. 686 - 707
• Main Authors: Steelman, L S, Abrams, S L, Whelan, J, Bertrand, F E, Ludwig, D E, Bäsecke, J, Libra, M, Stivala, F, Milella, M, Tafuri, A, Lunghi, P, Bonati, A, Martelli, A M, McCubrey, J A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2008; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Cancer Research; Cellular signal transduction; Chromosome 10; Chromosome translocations; Critical Care Medicine; Extracellular signal-regulated kinase; Gene mutations; Genetic aspects; Growth factor receptors; Growth factors; Health aspects; Hematology; Homology; Humans; Intensive; Internal Medicine; Kinases; Leukemia; Leukemia - etiology; Medicine; Medicine & Public Health; Mutation; Neoplasia; Neoplasms; Oncology; Phosphatase; Phosphatidylinositol 3-Kinases - metabolism; Protein Kinases - metabolism; PTEN Phosphohydrolase - metabolism; PTEN protein; Raf protein; review; Risk factors; Signal Transduction; STAT Transcription Factors - metabolism; Survival; Tensin; TOR protein; United States; inhibitors; Akt; PI3K; signal transduction; chemotherapeutic drugs; Raf
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2008.26

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.