ChemGenex Investigators Report Omacetaxine Effective in Killing CML Stem Cells in Animal Model Studies
The poster presentation was authored by Dr. Shaoguang Li and colleagues from the Jackson Laboratory in Maine, USA, as well as ChemGenex scientists.
The authors reported that omacetaxine reduced the number of leukemic stem cells in the bone marrow by more than 80% in an animal model of CML (mice with BCR-ABL-induced CML disease). In contrast, the tyrosine kinase inhibitor imatinib mesylate (Gleevec(R)) did not reduce the number of leukemic stem cells in the bone marrow. Previous research by Dr. Li and his colleagues found that the second generation tyrosine kinase inhibitor dasatinib (Sprycel(R)) did not eradicate CML stem cells in the same model system (Hu et al., 2006).
Consistent with the killing of CML stem cells, the authors reported that omacetaxine provided a significant survival benefit to mice with two different types of leukemia; BCR-ABL-induced CML and B cell acute lymphoblastic leukemia (B-ALL).
Scientists now believe that some cancers arise from a small number of aberrant cells that, like adult stem cells, have the ability to self-renew and differentiate into multiple cell types. These cells often persist in cancer patients in low numbers even following therapy, and can cause disease relapse. Therapies that effectively kill cancer stem cells as well as differentiated cancer cells may thus hold promise for improving the treatment of cancer and increasing survival from the disease.
The authors also reported that omacetaxine inhibited cell proliferation and markedly reduced the expression of the anti-apoptotic protein Mcl-1 in leukemic cell lines. Mcl-1 is a key target protein in several types of leukemias and other cancers, and is believed to be one of the major targets through which omacetaxine causes clinical responses.
"Following-on from the clinical data presented over the weekend, we are very pleased to be able to further articulate the underlying biology of omacetaxine's activity," said Dr. Greg Collier, ChemGenex's Managing Director and Chief Executive Officer. "We can now report that Mcl-1 is down-regulated by omacetaxine in CML, and that in an animal model the drug acts directly on leukemic stem cells in the bone marrow. These data suggest the potential of omacetaxine to be utilized across a range of leukemias, and support clinical application beyond CML, as well as the potential to extend disease-free survival in this disease."
Dr. Collier will host an investor conference call on Thursday, December 13 at 9:30am Australian Eastern Daylight Time (Wednesday, December 12 in the USA and Europe) to discuss the clinical results presented at ASH.
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Hu, Y. et al. (2006). Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice. PNAS. 103 (45), 16870-16875.
Ceflatonin(R) is a registered trade-mark of ChemGenex Pharmaceuticals Limited.
Gleevec(R)/Glivec(R) is a registered trade-mark of Novartis AG.
Sprycel(R) is a registered trademark of the Bristol-Myers Squibb Company.
About ChemGenex Pharmaceuticals Limited (http://www.chemgenex.com)
ChemGenex Pharmaceuticals is a pharmaceutical development company dedicated to improving the lives of patients by developing personalized oncology medicines. ChemGenex harnesses the power of genomics both to discover novel targets and drug compounds, and in clinical trials to develop more individualized treatment outcomes. ChemGenex's lead compound, omacetaxine mepesuccinate (formerly known as Ceflatonin(R)), is currently in phase 2/3 clinical trials for chronic myeloid leukemia (CML) where it has demonstrated single-agent efficacy against drug-resistant disease, as well as synergistic activity with the leading marketed compound. ChemGenex has a second anticancer compound, amonafide dihydrochloride (formerly known as Quinamed(R)) which is in phase 2 clinical development for various solid cancers, and a portfolio of assets in pre-clinical development. ChemGenex currently trades on the Australian Stock Exchange under the symbol "CXS" and on NASDAQ under the symbol "CXSP".
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Posted: December 2007