Alex's Lemonade Stand Foundation for Childhood Cancer

Background

Metastatic disease is responsible for about 90% of all cancer related deaths. Metastasis is when a patient's cancer has spread throughout the body and is not just located in one single tissue or organ. For children afflicted with metastatic osteosarcoma, the most common bone tumor in the pediatric population, it often means a very aggressive cancer that is associated with an extremely poor outcome.

Brain tumors are the most common solid tumors in children. High Grade Gliomas (HGG) constitute nearly 20% of all childhood brain tumors. These tumors are particularly difficult to treat and usually do not respond to even the most aggressive therapy, such that the expected survival seldom exceeds 24 months with less than 25% patients surviving 5 years from the diagnosis. It is therefore desirable to develop novel therapies that could improve these disappointing outcomes. Immune system based therapies have the potential to fulfill this dire need.

T-cell ALL is among the most frequent of child-hood leukemias, and a significant sub-set of patients are not effectively treated by conventional therapies. A subset of T-ALL with a particularly poor prognosis is associated with over-expression of the LYL1 gene, however, the role of LYL1 has been little studied. In this project, we propose to study the role of LYL1 in T-ALL. We have found that mice that lack the mouse Lyl1 gene show defective development of T-cells, which are the precursors of T-ALL leukemia.

Delay in blood cell count recovery after chemotherapy is the most commonly observed toxicity in pediatric acute myeloid leukemia (AML), and 80% of patients develop severe toxicities during treatment. Delay in therapy due to a low white blood cell (WBC) count places individuals at risk for severe infections, and is associated with an increased mortality. We are investigating genetic markers for risk for AML treatment-related toxicities, such as unexpectedly prolonged periods of low WBC count after chemotherapy.

Cancer is caused by the accumulation of errors (mutations) in the genetic material of tumor cells. The identification of these mutations has allowed the development of treatments specifically targeted at the mutated genes, resulting in remarkable clinical advances for a few types of cancer. These discoveries remain the exception rather than the rule, however, since only a minority of genes has been analyzed in most cancers.