By Peter W. Marks, MD, PhD
2009-12-08
During this morning’s Presidential
Symposium from 9:45 to 11:15 a.m. in Hall F, a view of what the future holds
for genomic medicine in hematology will be presented. ASH President Dr. Nancy
Berliner will chair this session, during which three scientific leaders in this
area will share their vision.
DNA sequencing has come a long way
since the seminal work of Maxam, Gilbert, and Sanger only a few decades ago.
Dr. Timothy Ley of Washington University
School of Medicine will review “next generation” sequencing technologies
applied to the discipline of hematology. By sequencing the genome of acute
myeloid leukemia (AML) samples and comparing them to normal matched genomes,
insight has been gained into critical genes involved in the pathogenesis of
this disease (New England Journal of Medicine, 2009; 361:1058-66). Both
familiar faces (NRAS and NPM1) and some new ones (mutations in the IDH1 gene)
were found to have an impact on prognosis. Importantly, these findings may soon
lead to therapeutic advances through provision of molecular targets common to
groups of individuals with AML.
In a similar vein, many advances
have been made in the past two decades in our ability to examine the function
of individual genes through knockout and knockdown technologies. Dr. Louis
Staudt from the Center for Cancer Research at the National Cancer Institute
will discuss elegant work using RNA interference-based genetic screens in order
to identify oncogenes as well as those genes that, while not mutated, are
essential for the development of neoplasia. Dr. Staudt’s work has had major
implications to date, particularly in the areas of lymphoma and multiple
myeloma. In describing the implications of the technique of RNA interference,
he notes in his profile on the Mantle Cell Lymphoma Consortium Web site that:
“Our current therapies are largely directed against cell proliferation and
survival pathways that are common to both malignant and normal cells, leading
to a lot of side effects. We hope this technology helps us find pathways that
are specifically required for lymphoma and not for normal cells, thereby
creating potential new targets for therapeutic intervention.”
To date, the development of many
drugs for the treatment of disease has relied on screening methodologies to
identify and refine candidate molecules from libraries of compounds. Dr. Todd
Golub from the Dana-Farber Cancer Institute, who is one of the founders of the
Broad Institute at MIT and Harvard, will discuss how advances in genomic
medicine are facilitating the development of genomic screening technologies
that can identify potential small-molecule candidates for the treatment of
hematologic malignancies.
Though at the end of the meeting,
these presentations should provoke the start of a fresh round of thinking about
what is possible through a genomic view of hematology and perhaps something to
present at the 2010 ASH Annual Meeting or other future meetings.
Dr. Marks indicated no relevant conflicts of interest.
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