PI3K/AKT/mTOR通路
癌症研究
PTEN公司
白血病
蛋白激酶B
MAPK/ERK通路
慢性粒细胞白血病
造血
干细胞
生物
医学
免疫学
信号转导
细胞生物学
作者
James A. McCubrey,Linda S. Steelman,Steven L. Abrams,F. E. Bertrand,D E Ludwig,Jörg Bäsecke,Massimo Libra,Franca Stivala,Michèle Milella,Agostino Tafuri,Paolo Lunghi,Antonio Bonati,Alberto M. Martelli
出处
期刊:Leukemia
[Springer Nature]
日期:2008-03-13
卷期号:22 (4): 708-722
被引量:230
摘要
The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are frequently activated in leukemia and other hematopoietic disorders by upstream mutations in cytokine receptors, aberrant chromosomal translocations as well as other genetic mechanisms. The Jak2 kinase is frequently mutated in many myeloproliferative disorders. Effective targeting of these pathways may result in suppression of cell growth and death of leukemic cells. Furthermore it may be possible to combine various chemotherapeutic and antibody-based therapies with low molecular weight, cell membrane-permeable inhibitors which target the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to ultimately suppress the survival pathways, induce apoptosis and inhibit leukemic growth. In this review, we summarize how suppression of these pathways may inhibit key survival networks important in leukemogenesis and leukemia therapy as well as the treatment of other hematopoietic disorders. Targeting of these and additional cascades may also improve the therapy of chronic myelogenous leukemia, which are resistant to BCR-ABL inhibitors. Furthermore, we discuss how targeting of the leukemia microenvironment and the leukemia stem cell are emerging fields and challenges in targeted therapies.
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