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Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-03-0860.
Submitted March 20, 2003
Accepted July 21, 2003
Inhibition of acute lymphoblastic and myeloid leukemias by a novel kinase inhibitor
Thomas Grunberger, Peter Demin, Olga Rounova, Nigel Sharfe, Lorand Cimpean, Harjit Dadi, Andrew Freywald, Zeev Estrov, and Chaim M Roifman*
Division of Immunology and Allergy, Department of Pediatrics. Infection, Immunity, Injury, and Repair Program, Research Institute, Hospital for Sick Children and the University of Toronto, Toronto, ON, Canada
Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
* Corresponding author; email: croifman{at}sickkids.ca.
In recent years, synthetic tyrosine kinase inhibitors have made a rapid transition from basic research to therapeutic application. These compounds represent a major clinical advance in the approach to cancer in their relative specificity of action and decreased toxicity. We report here the development of a novel tyrosine kinase inhibitor CR4 that interferes with growth promoting pathways to effectively inhibit the growth and survival of both Philadelphia positive and negative Acute Lymphoblastic Leukemia (ALL) as well as Acute Myeloid Leukemia (AML). While efficiently ablating leukemic cell growth, normal cell growth and differentiation remains unaffected by CR4. CR4 demonstrates an ability to inhibit the function of multiple growth-critical kinases, and yet exhibits a low level of cytotoxicity. These findings suggest that CR4 may prove to be highly effective as a therapeutic agent.
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