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Complete remission of TEL-PDGFRB–induced myeloproliferative disease in mice by receptor tyrosine kinase inhibitor SU11657
Journal article   Peer reviewed

Complete remission of TEL-PDGFRB–induced myeloproliferative disease in mice by receptor tyrosine kinase inhibitor SU11657

Jennifer A Cain, Jay L Grisolano, A. Douglas Laird and Michael H Tomasson
Blood, Vol.104(2), pp.561-564
07/15/2004
DOI: 10.1182/blood-2003-11-3801
PMID: 15044254

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Abstract

Abstract The TEL-PDGFRB fusion oncogene is associated with chronic myelomonocytic leukemia (CMML) and results in the expression of a constitutively active tyrosine kinase. SU11657 is a multitargeted selective inhibitor of class III/V receptor tyrosine kinases, including the platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) receptors KIT and FLT3. SU11657 inhibited TEL/PDGFβR kinase activity at nanomolar concentrations and inhibited TELPDGFRB-mediated factor-independent growth in myeloblastic 32D cells. Daily oral administration of SU11657 at 40 mg/kg suppressed myeloproliferation and significantly prolonged survival in TELPDGFRB mice treated prior to disease development, as well as in those with large tumor burdens. Our findings suggest that SU11657 or similar agents may have therapeutic potential in humans with hematologic malignancies expressing PDGFR fusion oncogenes. (Blood. 2004;104:561-564)

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