A03 Evolution of the regulatory landscape in hematopoietic malignancies
Epigenetic mechanisms are central for transcriptional regulation and mediate adaptation to changing environmental settings. How epigenetic changes influence cancer evolution is currently unclear.
We want to determine the regulatory landscape of human AML by investigating enhancer chromatin modifications (H3K27ac) in AML diagnosis and relapse samples.These studies will uncover the important regulatory regions that are critical for AML development and progression, and may therefore, in the future, lead to novel therapeutic strategies for AML treatment.
Figure legend: Molecular events contributing to evolution of AML. Normal cells accumulate genetic mutations in oncogenes and tumor suppressor genes which lead to abnormal proliferation and onset of AML. Genetic mutations are not the only change in AML; an altered regulatory landscape is likely to affect the transcriptional network in AML cells. After diagnosis, AML is treated with chemotherapy which eventually eradicates the vast amount of AML cells. However, some subclones may resist chemotherapy, additional mutation may confer resistance to therapy and changes in the regulatory landscape of AML cells may help in adapting to the changed environmental settings. Therefore, in order to understand evolution of AML it is necessary to analyze both genetic and epigenetic changes in relapsed AML.