Childhood Cancer

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Identification of New Therapeutic Targets in Pediatric Acute Lymphoblastic Leukemia Through Mosaic Trisomy and Aneuploidy-Based Synthetic Lethality Screens

Institution: 
Dana-Farber Cancer Institute
Researcher(s): 
David Pellman
Grant Type: 
Innovation Grants
Year Awarded: 
2010
Type of Childhood Cancer: 
Acute Lymphoblastic Leukemia (ALL)
Project Description: 

Leukemia is the most common type of cancer in children. Despite significant improvements in therapy over the past four decades, leukemia is still a leading cause of cancer-related death among children and young adults. Further improvements in leukemia therapy need to be built on a better understanding of the basic biology of cancer.  A common feature of many types of cancer, including leukemia, is an abnormal number of chromosomes. An extra copy of chromosome 21, known as trisomy 21, is a hallmark of pediatric acute lymphoblastic leukemia (ALL). Despite its prevalence, how an extra copy of chromosome 21 promotes leukemia is a mystery.    We developed a new method for studying the effects of extra chromosomes on cells, which involves collecting cells from rare individuals who are born with a mix of normal cells and cells with an extra copy of one chromosome.  Aside from the different numbers of chromosomes, cells from these patients are identical. We have developed a procedure to separate normal cells from the cells with an extra chromosome. 

We plan to investigate how trisomy 21 affects the behavior of cells by comparing these two populations of nearly identical cells. We also plan to identify methods to target and specially kill the cells with the extra chromosome, but not the normal cells.  We anticipate that this system will provide new opportunities and avenues to address the question of how chromosome number relates to cancer, and also may lead to novel therapies for ALL and other types of cancer.