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
Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Leukemia. 2008 Apr;22(4):686-707. doi: 10.1038/leu.2008.26. Epub 2008 Mar 13.
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.
白血病细胞中会发生突变和染色体易位，导致各种生长因子受体及下游激酶的表达升高或组成性激活。Raf/MEK/ERK、PI3K/PTEN/Akt/mTOR和Jak/STAT信号通路常因上游基因的突变而被激活。Raf/MEK/ERK和PI3K/PTEN/Akt/mTOR信号通路受上游Ras调控，而Ras在人类癌症中常发生突变。最近发现，FLT-3和Jak激酶以及10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）磷酸酶在某些造血系统肿瘤中也常发生突变或其表达发生改变。Raf/MEK/ERK、PI3K/PTEN/Akt/mTOR和Jak/STAT信号通路引发的许多事件对生存信号通路有直接影响。生存信号通路的异常调控可导致细胞生长失控并引发白血病。在本综述中，我们描述了Raf/MEK/ERK、PI3K/PTEN/Akt/mTOR和Jak/STAT信号级联反应，并总结了有关这些信号通路的调控、突变状态及其与白血病关系的最新数据。
