Principal Investigator/Program Director: Timothy J. Ley, MD. tley@im.wustl.edu Washington University Medical School, Box 8007
660 South Euclid, St Louis, Mo 63110-1092
Ph 314-362-8831, Fax 314-362-9333
Goals and
Significance The long-term goal of this program project is to
define all the genetic alterations 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 clinical
outcomes, since these are the ones most likely to have an impact on therapy.
We will use this information to create molecular diagnostic tools for disease
stratification, and 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 pathogenesis of this disease.
The Key Elements of the Program Project
The systematic study of adult AML genomics requires a unique institutional environment with specific key elements.
Our group is in a unique position to perform these studies because these components
are already in place at Washington University Medical School and Barnes Jewish Hospital
(Figure 1). The first component is the Siteman Cancer Center (SCC), designated by the
NCI in 2001. The SCC has created a critical infrastructure that includes 12 Cores that
will support the science in the Genomics of AML Program Project Grant (GAML PPG).
The second key component is the Washington University Genome Sequencing Center
(GSC), whose Director is Rick Wilson, leader of Project 1.
The
GSC is one of the largest academic sequencing centers in the world,
and is currently performing 30 million sequencing reactions per
year. The techniques and capacity for large scale resequencing
of AML samples is therefore available at our GSC. The third key
component is the availability of large numbers of AML patients
via the Leukemia/Stem Cell Transplantation Program at Washington
University, headed by John DiPersio, leader of Project 3. This
program is one of the largest of its kind in the United States,
performing more than 250 stem cell transplants each year, and
entering more than 75 new AML patients on protocols. Patient
material crucial for validating the importance of AML-associated
mutations will also come from the Leukemia Tissue Bank of Cancer
and Leukemia Group B (CALGB) and from the NCI’s Cancer Therapy
Evaluation Program (CTEP). The final component is mouse modeling
of AML, which is critical for the validation of genes that are
implicated in AML pathogenesis. One of the first mouse models of
an acute myeloid leukemia was established at this institution by
the PI of the GAML PPG, and several project leaders have
successfully created important mouse models of this disease.
Under the auspices of the GAML PPG, these components will be
harnessed to improve our understanding of AML genomics, which
will hopefully lead to improvements in therapy.
Home
| Microarray Data
| Search
| Software
| Publications
| Collaborative Projects
