Growth factors leukemia

Inhibition of hematopoietic growth factors Imatinib (Glivec ) is applied to treat chronic myeloid leukemia in Philadelphia-chromosome positive patients. In these patients, translocation of parts of chromosomes 9 and 22 results in the expression of a fusion protein with increased tyrosine kinase activity, called Bcr-Abl. Imatinib is a small Mw inhibitor selective for the tyrosine kinase activity of Bcr-Abl. Thereby, it inhibits the Bcr-Abl induced cell cycle progression and the uncontrolled proliferation of tumor cells. 

Itoh K, Friel J, Laker C, Zeller W, Just U, Bittner S, Nibbs RJ, Harrison P, Nishikawa S I, Mori KJ, Ostertag W, 1997. The role of soluble growth factors and of stroma cells in inducing transient growth and clonal extinction of stroma cell dependent erythroblastic leukemia cells. Leukemia 11 1753... 

Cyclin-dependent kinase 2 Chronic myelogenous leukemia Dose-limiting toxicity Epidermal growth factor Epidermal growth factor receptor HER-2 HER-3 HER-4... 

Fig. 11.2. Domain structure of cytokine receptors. Schematic representation of the domain structure of selected cytokine receptors. WS motif conserved WSXWS sequence (W tryptophan S serine X non-conserved amino add) IL interleukin EpoR receptor for erythropoietin GHR growth hormone receptor LIF-R leukemia inhibitory factor receptor G-CSFR granulocyte colony stimulating factor receptor IFNR interferon receptor TNFR tumor necrosis factor receptor NGFR nerve growth factor receptor Fas, CD40 transmembrane receptors of lymphocytes.

Taya, S., Inagaki, N., Sengiku, H., Makino, H., Iwamatsu, A., Urakawa, I., Nagao, K., Kataoka, S., and Kaibuchi, K. (2001). Direct interaction of insulin-like growth factor-1 receptor with leukemia-associated RhoGEF. J. Cell Biol. 155, 809-820. 

Kamohara H, Takahashi M, Ishiko T, Ogawa M, Baba H. 2007. Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-alpha and leukemia inhibitory factor in pancreatic carcinoma cells Impact of CXCL-8 as an autocrine growth factor. Int J Oncol 31 627-632. 

Imatinib (STI571) is an inhibitor of the tyrosine kinase domain of the Bcr-Abl oncoprotein and prevents the phosphorylation of the kinase substrate by ATP. It is indicated for the treatment of chronic myelogenous leukemia (CML), a pluripotent hematopoietic stem cell disorder characterized by the t(9 22) Philadelphia chromosomal translocation. This translocation results in the Bcr-Abl fusion protein, the causative agent in CML, and is present in up to 95% of patients with this disease. This agent inhibits other activated receptor tyrosine kinases for platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF), and c-kit. 

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