Anti-Hormonal Approach to Leukemia Cytokine Receptor

Approximately half of the individuals diagnosed with cancer will die of the disease even if the receive the best therapies that modern medicine has to offer. In addition, even with current therapies, including surgery, radiation, and chemotherapy induced remission, the side effects are ravaging and reduce "quality of life" to an unacceptable level. Obviously, new therapeutic approaches are needed which are more specific, less damaging and more effective. Several years of leukemia research has led the principal investigator to a hypothesis that many cancers remain hormone-dependent, retain the ability to terminally differentiate, and exhibit many normal cell properties. The present study was initiated to exploit on of these properties, namely hormone sensitivity of leukemia cells, in an effort to develop a lineage specific, gentle, safe and effective drug which will destroy leukemia cells. In particular, a drug will be devised which will specifically bind erythropoietin, and in doing so will competitively inhibit growth of leukemia cells which will specifically bind hormone for their survival and proliferation. The drug will be composed of the exoplasmic domain of the Epo receptor which will be expressed and purified through recombinant DNA technology. In Phase I, we will subclone the EpoR gene sequences which encode the Epo binding domain. This will be expressed in E. coli and purified by ligand affinity columns. Its ability to kill Epo-dependent cell lines by competitive inhibition will be tested. If feasibility of this approach is confirmed, Phase II will attempt to prove the efficacy of soluble Epo receptors to inhibit growth of Epo-dependent leukemia in the animal models.