Scott A. Armstrong, MD, PhD
The Armstrong lab uses genome wide approaches to characterize leukemia development, and to develop new therapeutic approaches. The rapid progress in the fields of genomics, drug development, and stem cell biology provide an unprecedented opportunity to develop new therapeutics for cancer. This is particularly true for leukemias where we can now define leukemia development in the context of a detailed understanding of normal blood cell development. We have used genomic approaches to characterize different subtypes of childhood leukemia, and demonstrate that acute lymphoblastic leukemias (ALL) with rearrangement of the MLL gene on chromosome 11q23 (MLL-ALL) have a highly distinct gene expression pattern as compared to other ALLs. We also demonstrated that MLL-ALL depends upon activation of the receptor tyrosine kinase FLT3. These studies have prompted clinical assessment of FLT3 inhibitors in MLL-ALL. We have also generated mouse models of leukemia that have proven useful both for understanding mechanisms of leukemogenesis, and for testing new therapeutics. Using these models we have identified leukemia stem cells in acute myelogenous leukemia and determined pathways responsible for leukemic self-renewal. Furthermore, we have recently demonstrated that specific histone methyltransferases maintain leukemogenic gene expression programs that are critical for leukemia self-renewal and survival. These studies have prompted ongoing clinical trials assessing histone methyltransferase inhibitors in patients with hematologic malignancies. We feel genome wide technologies will continue to provide a better understanding of the differences between normal and cancer cells that will lead to more precise/targeted approaches to cancer therapy.