Genetic and Epigenetic Determinants of Chemotherapy Resistance and Adverse Outcome in Elderly Patients With AML
- Delineate the spectrum of genetic and epigenetic lesions occurring in elderly patients
with acute myeloid leukemia (AML).
- Determine the biological functions perturbed by these lesions.
- Identify and validate lesions or pathways that are most highly associated with
chemo-sensitive and chemo-refractory disease, and with adverse outcome in elderly AML.
- Identify potential classifiers and biomarker lesions that we can then evaluate
prospectively in the E2906 trial which is about to begin enrollment.
OUTLINE: DNA and RNA extracted from cell samples are analyzed for genetic and epigenetic
expression by Agilent SureSelect sequencing, Illumina HiSeq2000 platform coding and
sequencing, DNA methylation, and microarray assays. Results are then associated with
patients' overall survival, progression-free survival, and complete response rate. Results
are also analyzed assessing the prognostic relevance of known mutations and epigenetic
alterations that have shown to have an impact on overall survival and response to therapy in
younger patients with acute myeloid leukemia (AML) in E1900 including, but not limited to,
FLT3, DNMT3A, IDH1, IDH2, TET2, ASXL1, WT1, and MLL, and 15-gene DNA methylation classifier,
and with novel recurrent mutations identified by other AML-profiling efforts.
Genetic and epigenetic determinants of chemoresistance and adverse outcomes
Ross Levine, MD
Memorial Sloan-Kettering Cancer Center