The JAK-STAT pathway: A therapeutic target in hematological malignancies

被引：76

作者：

Ferrajoli, A. ^{[1
]}

Faderl, S. ^{[1
]}

Ravandi, F. ^{[1
]}

Estrov, Z. ^{[1
]}

机构：

[1] Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX USA

来源：

CURRENT CANCER DRUG TARGETS | 2006年 / 6卷 / 08期

关键词：

JAK-STAT pathway; hematological malignancies; targeted therapy;

D O I：

10.2174/156800906779010227

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The development and function of hematopoictic cells depends on complex signaling pathways that are mediated by numerous cytokines and their receptors. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is prominent both in normal hematopoiesis and in hematological malignancies. SATs are phosphorylated on tyrosine residues via JAK kinases and on serine residues by a variety of scrine/threonine kinases. STATs then dimerize, translocate to the nucleus and bind DNA, initiating the transcription of target genes. STAT proteins mediate cell growth, differentiation, apoptosis, transformation, and other fundamental cell functions. Recently, mutations in the JAK2 gene driving the proliferation of the neoplastic clone have been identified in myeloproliferative disorders. In addition constitutive activation of the JAK-STAT pathway has been reported in various types of leukemias such as acute myelogenous leukemia, T-LGL leukemia, and multiple myeloma. This review describes the pathophysiological role of this pathway in hematological malignancies and the potential benefits of JAK-STA'I' inhibition.

引用

页码：671 / 679

页数：9

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