Alex's Lemonade Stand Foundation for Childhood Cancer

Background

The mutation FLT3/ITD is common in acute myeloid leukemia (AML) and results in over-activation of cell signaling causing enhanced cell proliferation and survival. Patients with FLT3/ITD have a poor prognosis. The role of FLT3 inhibitors as targeted therapy is currently being evaluated in children and adults with AML. Despite an initial response, many patients relapse as the leukemic cells develop new mechanisms to survive and resist the effects of the targeted therapy. This group of patients has very few treatment options and very poor survival.

Background

Childhood cancer survival rates have improved markedly, with an estimated >325,000 survivors in the U.S. today. However, survivors have an increased risk of later adverse health outcomes such as cardiopulmonary disease, second cancers, and possibly fractures, likely due to the effects of chemotherapy, radiation exposure, or other therapies.

AML is a blood cancer from which most patients will eventually die despite aggressive therapy. It is thought that only a minute population of cancer cells ("leukemia stem cells" or LSCs) causes/maintains the leukemia. Thus, there is great interest in understanding LSCs to develop novel treatments that specifically destroy these cells. LSCs may be diverse across patients: in some, they may resemble a normal blood stem cell whereas in others, they may look like a maturing white blood cell.

Acute myeloid leukemia (AML) represents a heterogeneous group of malignancies with great variability in clinical course and response to therapy. Currently, cytogenetics is the most important prognostic factor in this disease. In recent years, an increasing list of molecular markers with prognostic significance in AML has been identified; nonetheless, new prognostic markers and therapeutic targets are still needed.

While much success in the treatment of pediatric cancers has been obtained over the past 20 years by optimizing the use of previously discovered chemotherapies, new agents are desperately needed to cure those patients who do not respond to current therapy. DNA mutations and structural abnormalities in chromosomes contribute to cancer formation by improperly regulating genes in the cell. Another mechanism by which genes become misregulated in cancer is through aberrant DNA methylation.