Childhood Cancer Research
Fred Hutchinson Cancer Research Center
Seattle, WA 98109-1024
United States
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
Bone marrow blood stem cell transplants are used in the treatment of leukemias and other diseases of the blood and immune system. Unfortunately, use of this therapy is limited for some patients due to lack of appropriate donors for stem cells or insufficient numbers of stem cells.
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.
Background
The aim of the National Cancer Institute supported Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative is to use next generation sequencing tools to develop new, more effective treatments for childhood cancers including pediatric acute myeloid leukemia (AML). The genetic changes that drive leukemia cells are different in children and adults, therefore, it's important to study pediatric cancers separately.
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.
AML, the second most common blood cancer in children, is a form of leukemia which is extremely difficult to treat. Nearly half of all children diagnosed with AML will not be cured. This includes many patients whose leukemia will initially respond to chemotherapy, only to return (or 'relapse') at a later time. With currently available treatments, cure rates for relapsed AML remain very low. Improved methods of predicting and detecting relapse, combined with improved leukemia treatments, are urgently needed. It is with this in mind that our laboratory studies the WT1 gene.
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.
Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with approximately 2400 new cases/year in the United States. Patients are put into remission using chemotherapy, and over 70% stay in remission. If a patient relapses, it is hard to achieve a long-term cure, and they often succumb to their disease. The best chance for maintaining a remission after relapse is often through a stem cell transplant (SCT), in which the patient's bone marrow is replaced with hematopoietic stem cells (HSC) from either a donor or cord blood unit.
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.
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