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| Genomics Of AML Summary
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When a person is in good health, blood cells are made in an orderly and controlled fashion. In leukemia the cells that are involved in fighting infections and preventing excess bleeding are no longer being produced correctly. There are four major types of leukemias that are characterized by the speed at which they progress and the type of blood cells involved. Acute myelogenous leukemia (AML) is one of the four primary leukemias and nearly 12,000 new cases are diagnosed each year in the United States. With chemotherapy, remission is achieved in 50-80% of the patients with newly diagnosed AML. Unfortunately, despite treatment, the leukemia returns for the majority of these patients. There is much evidence that several pretreatment factors including age, white blood cell count and the leukemic cell DNA content and structure can aid in predicting which patient will suffer a poor outcome or which will be able to survive free of disease. However, much more study is needed, so that these clues will allow us to make better predictions and to identify alternative treatments that may enhance survivability.
The long-term goal of the "Genomics of AML" program project is to define all the DNA changes that occur in adult AML cells, and to define the importance of these mutations for disease susceptibility, initiation, progression, relapse, and resistance. The short-term goal is to define the most frequently occurring mutations that affect outcomes from treatment, since these are the ones most likely to have an impact on therapy. We will use this information to create better molecular diagnostic tools and to identify candidate genes for targeted therapeutics. The identification of the mutations that occur in adult AML genomes will contribute greatly to our understanding of the development of this disease.
This large research effort, led by Dr. Timothy Ley, is taking place at the Washington University School of Medicine and it takes full advantage of this unique institutional environment. The Genome Sequencing Center has the technology, capacity and the computing power for large scale re-sequencing of hundreds of AML samples and the subsequent analysis of the data generated. The Washington University Siteman Cancer Center has an infrastructure that includes 12 core facilities to support the science; ranging from the ability to collect and bank tissue samples to assisting in complex statistical analysis. The third key component is the availability of large numbers of AML patients via the Leukemia/Stem Cell Transplantation Program at Washington University. This program is one of the largest of its kind in the United States, performing more than 250 stem cell transplants each year. The final component is the use of genetically modified mice that develop AML. Specific gene mutations discovered from the sequencing data can be validated and studied further through the use of the AML mice. All of these components will be harnessed to improve our understanding of AML genomics, which will hopefully lead to improvements in leukemia therapy. |
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