Discovery and validation of biomarkers to myeloid leukemia cancer stem cells by the generation of monoclonal antibodies
The aim of this proposal is to identify new biomarkers by the generation of specific monoclonal antibodies specific to the Chronic Myeloid Leukemia – Blast Crisis (CML-BC) and Acute Myeloid Leukemia (AML) Cancer Stem Cells (CSC). Cancer stem cells arise from normal stem and progenitor cells though a number of gene mutations. The CSC is a small population of cells within the tumor that drives its growth. Most cells in the tumor are derived from the cancer stem cell, however they do not have growth potential. The CSC are also responsible for the recurrence of the disease following treatment. Since these cells are very resistant to current chemotherapies, treatment will only be successful if the CSC is targeted and eliminated. By defining the characteristic cell surface markers on these cells, scientists will be able to isolate them and study their properties. Discovery of novel biomarkers will not only be useful to study cancer stem cell biology, but may also be useful clinically as a diagnostic for diagnosis or as a prognostic indicator. Identification of cell surface targets in CSC may also lead to the development of new, highly specific targets for therapy.
Myeloid leukemias are devastating diseases especially in the elderly who can not tolerate intensive chemotherapeutic treatments. The aim of this research proposal is to discover and validate new biomarkers through the generation of monoclonal antibodies specific to the acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cancer stem cells (CSC) which are not present on the normal hematopoietic stem cell (HSC). Known cell surface characteristics of these myeloid CSC are similar to normal stem and progenitor cells. Specific markers to the CSC that distinguish them from the normal HSC have not yet been identified. Discovery of novel biomarkers will not only be useful to study cancer stem cell biology, but may also be useful clinically as a diagnostic for confirmatory diagnosis or as a prognostic indicator. Identification of cell surface targets or active gene pathways in CSC but not normal HSC may lead to the development of new, highly specific targets for therapy. Approximately 3000 cases of myeloid leukemia will be diagnosed in the state of California in 2008 according to National Cancer Institute estimates. With current therapies, the 5 year survival rate for acute myeloid leukemia is 21%. Improved cancer diagnosis and treatment would directly benefit the people of California.