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The Johns Hopkins University School of Medicine

Office of Research Administration733 North BroadwayBRB, Suite 117
Baltimore, MD 21205
United States

Several common childhood leukemias are now considered curable. However, there are features of leukemia cells which continue to make them difficult to treat. One such feature is having an alteration in a gene called MLL. It is not yet fully understood why MLL alterations cause leukemia. In addition, current therapies do not seem as effective against leukemia with MLL alterations as it is in those without. We hope to better understand MLL in a way that will bring about new therapies for the disease. Our own body can destroy cancer cells with the help of tumor suppressor genes.

An individual's immune system should be capable of recognizing growing tumor cells as foreign and destroy them, as is done with viral and bacterial infections. Evidence for this in humans includes the spontaneous regression of certain cancers such as neuroblastoma. One possible explanation for why this does not happen with all cancers is that growing tumors do not provide a danger signal to the immune system, and thus, do not activate the immune system to kill.

Background


To determine promoter and genome-wide patterns of methylation alterations in AML and high-risk sarcoma samples from known clinical/molecular subgroups. We hypothesize that tumor samples with known adverse prognostic features will have distinct regional changes in CpG methylation when compared to lower-risk counterpart samples. To test this hypothesis, we are developing novel methods to prepare detailed, genome-wide maps of methylation in high risk pediatric cancer samples using a novel method of enrichment of methylated followed by high-resolution genomic tiling microarray analysis.

AML is the 3rd leading cause of cancer related death in children. Despite treatment intensification, only approximately half of children survive their disease.

Background


Leukemia is the most common childhood cancer worldwide with almost 4,000 cases each year in the United States alone. Acute lymphoblastic leukemia (ALL) is cancer of the white blood cells and T-cell leukemia is a particularly aggressive subtype of leukemia that involves T-cells or white cells that develop in the thymus. T-cell ALL constitutes about 13-15% of all cases of childhood ALL.

 

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