Targeting mutated tyrosine kinases in the therapy of myeloid leukaemias
- 1 June 2004
- journal article
- review article
- Published by Informa Healthcare in Emerging Therapeutic Targets
- Vol. 8 (3), 221-239
- https://doi.org/10.1517/14728222.8.3.221
Abstract
Myeloid leukaemias are frequently associated with translocations and mutations of tyrosine kinase genes. The products of these oncogenes, including BCR-ABL, TEL-PDGFR, Flt3 and c-Kit, have elevated tyrosine kinase activity and transform haematopoietic cells, mainly by augmentation of proliferation and enhanced viability. Activated ABL kinases are associated with chronic myeloid leukaemia. Mutations in platelet-derived growth factor receptor beta are associated with chronic myelomonocytic leukaemia. Flt3 or c-Kit cooperate with other types of oncogenes to create fully transformed acute leukaemias. Elevated activity of these tyrosine kinases is crucial for transformation, thus making the kinase domain an ideal target for therapeutic intervention. Tyrosine kinase inhibitors for various kinases are currently being evaluated in clinical trials and are potentially useful therapeutic agents in myeloid leukaemias. Here, the authors review the signalling activities, mechanism of transformation and therapeutic targeting of several tyrosine kinase oncogenes important in myeloid leukaemias.Keywords
This publication has 103 references indexed in Scilit:
- Approaches for the sequence-specific knockdown of mRNANature Biotechnology, 2003
- Effect of the Tyrosine Kinase Inhibitor STI571 in a Patient with a Metastatic Gastrointestinal Stromal TumorNew England Journal of Medicine, 2001
- Molecular genetics of acute myeloid leukaemiaBest Practice & Research Clinical Haematology, 2001
- Lipid phosphatases in the immune systemSeminars in Immunology, 2000
- Growth inhibition and modulation of kinase pathways of small cell lung cancer cell lines by the novel tyrosine kinase inhibitor STI 571Oncogene, 2000
- An intramolecular SH3-domain interaction regulates c-Abl activityNature Genetics, 1998
- Direct Association of Csk Homologous Kinase (CHK) with the Diphosphorylated Site Tyr568/570 of the Activated c-KIT in MegakaryocytesPublished by Elsevier BV ,1997
- Redox modulation of tyrosine phosphorylation-dependent signal transduction pathwaysFree Radical Biology & Medicine, 1996
- A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycleCell, 1993
- Mice homozygous for the ablm1 mutation show poor viability and depletion of selected B and T cell populationsCell, 1991