Scott Armstrong uses genomic approaches to characterize human leukemia, while developing murine models to test hypotheses generated by these studies.

Dr. Armstrong recently demonstrated that acute lymphoblastic leukemias with rearrangement of the MLL gene on chromosome 11q23 have a highly distinct gene expression pattern as compared to other acute lymphoblastic leukemias (ALL). Based on these data, he hypothesizes that the difference in gene expression is the reason for the poor response to standard ALL therapy, and that the dramatic difference in gene expression is due to this leukemia arising from a different cell of origin. The gene that best distinguished MLL from other acute leukemias was FLT3. Armstrong and colleagues have subsequently shown that FLT3 is constitutively active in MLL, and that a small molecule inhibitor of FLT3 is active against the disease in vivo. More recently they have shown that 20% of children with ALL whose disease will ultimately relapse have leukemia harboring a FLT3 mutation. These discoveries have led to the development of a clinical trial assessing FLT3 inhibitors in relapsed acute leukemia.

Dr. Armstrong's lab is developing mouse models of MLL induced leukemogenesis for the testing of new therapeutic approaches. They are also involved in the biological questions that will be addressed in a FLT3 inhibitor trial. These fundamental studies, along with the ongoing clinical trial with FLT3 inhibitors, provide an excellent opportunity to improve upon current therapies for patients with leukemia.