Abstract
Collaboration in Cancer Drug Trials, 2012 Chabner Colloquium
Highlights
This presentation will describe the discovery of a new class of acute leukemias that share in common disruption of a novel gene regulatory mechanism that involves alterations in 5-hydroxymethylcytosine (5hmC). 5hmC is a newly discovered epigenetic mark that plays a key role in gene activation, whereas the better-known DNA methylation epigenetic mark is mostly associated with gene silencing
TET2 loss of function mutants partially reproduce the effects of Isocitrate Dehydrogenase (IDH) mutations, explaining why these two types of mutations are mutually exclusive in leukemia patients
We observed that RAF inhibitors led to complete suppression of MAPK signaling in BRAF mutant melanomas, but only to transient inhibition of MAPK signaling in BRAF mutant colorectal cancers (CRCs), likely explaining their insensitivity
Summary
This presentation will describe the discovery of a new class of acute leukemias that share in common disruption of a novel gene regulatory mechanism that involves alterations in 5-hydroxymethylcytosine (5hmC). 5hmC is a newly discovered epigenetic mark that plays a key role in gene activation, whereas the better-known DNA methylation epigenetic mark is mostly associated with gene silencing. Mice containing mutant IDH or TET2 in their bone marrow cells develop preleukemic syndromes with similar epigenetic defects as the human disease. It is possible to design inhibitors that inhibit mutant forms of IDH, which may restore normal programming of gene expression and kill leukemia cells.
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