Targeting Signal Transducer and Activator of Transcription Signaling Pathway in Leukemias

被引:117
作者
Benekli, Mustafa
Baumann, Heinz
Wetzler, Meir [1 ]
机构
[1] Roswell Pk Canc Inst, Dept Med, Leukemia Sect, Buffalo, NY 14263 USA
关键词
ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; COLONY-STIMULATING FACTOR; RETINOIC ACID RECEPTOR; DNA-BINDING ACTIVITY; CELL-CYCLE ARREST; CONSTITUTIVE ACTIVATION; ARSENIC TRIOXIDE; STAT PROTEINS; FUSION PROTEIN;
D O I
10.1200/JCO.2008.21.3264
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Signal transducer and activator of transcription (STAT) proteins comprise a seven-member family of latent cytoplasmic transcription factors that are activated through tyrosine phosphorylation by a variety of cytokines and growth factors. Aberrant activation of STATs accompanies malignant cellular transformation with resultant leukemogenesis. Constitutive activation of STATs has been demonstrated in various leukemias. A better understanding of the mechanisms of dysregulation of the STAT pathway and understanding of the cause and effect relationship in leukemogenesis may serve as a basis for designing novel therapeutic strategies directed against STATs. Mechanisms of STAT activation, the potential role of STAT signaling in leukemogenesis, and recent advances in drug discovery targeting the STAT pathway are the focus of this review.
引用
收藏
页码:4422 / 4432
页数:11
相关论文
共 118 条
  • [51] Stat3 isoforms, α and β, demonstrate distinct intracellular dynamics with prolonged nuclear retention of stat3β mapping to its unique C-terminal end
    Huang, Ying
    Qiu, Jihui
    Dong, Shuo
    Redell, Michele S.
    Poli, Valeria
    Mancini, Michael A.
    Tweardy, David J.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (48) : 34958 - 34967
  • [52] ERBB receptors and cancer: The complexity of targeted inhibitors
    Hynes, NE
    Lane, HA
    [J]. NATURE REVIEWS CANCER, 2005, 5 (05) : 341 - 354
  • [53] P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members
    Ilaria, RL
    VanEtten, RA
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (49) : 31704 - 31710
  • [54] A new RING for SUMO: wrestling transcriptional responses into nuclear bodies with PIAS family E3 SUMO ligases
    Jackson, PK
    [J]. GENES & DEVELOPMENT, 2001, 15 (23) : 3053 - 3058
  • [55] Targeting Stat3 in cancer therapy
    Jing, N
    Tweardy, DJ
    [J]. ANTI-CANCER DRUGS, 2005, 16 (06) : 601 - 607
  • [56] Rational drug design of G-quartet DNA as anti-cancer agents
    Jing, NJ
    Sha, W
    Li, YD
    Xiong, WJ
    Tweardy, DJ
    [J]. CURRENT PHARMACEUTICAL DESIGN, 2005, 11 (22) : 2841 - 2854
  • [57] Aberrant methylation of the negative regulators RASSFIA, SHP-1 and SOCS-1 in myelodysplastic syndromes and acute myeloid leukaemia
    Johan, MF
    Bowen, DT
    Frew, ME
    Goodeve, AC
    Reilly, JT
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2005, 129 (01) : 60 - 65
  • [58] Regulation of interferon-gamma-activated STAT1 by the ubiquitin-proteasome pathway
    Kim, TK
    Maniatis, T
    [J]. SCIENCE, 1996, 273 (5282) : 1717 - 1719
  • [59] Systemic interferon-α (IFN-α) treatment leads to Stat3 inactivation in melanoma precursor lesions
    Kirkwood, JM
    Farkas, DL
    Chakraborty, A
    Dyer, KF
    Tweardy, DJ
    Abernethy, JL
    Edington, HD
    Donnelly, SS
    Becker, D
    [J]. MOLECULAR MEDICINE, 1999, 5 (01) : 11 - 20
  • [60] Koistinen P, 1997, ACTA HAEMATOL-BASEL, V98, P14