Genetic Basis of High-risk Childhood Cancer Points to Possible New Drug Treatment Strategy
Research led by St. Jude Children’s Research Hospital scientists has identified a possible lead in treatment of two childhood leukemia subtypes known for their dramatic loss of chromosomes and poor treatment outcomes.
The findings also provide the first evidence of the genetic basis for this high-risk leukemia, which is known as hypodiploid acute lymphoblastic leukemia (ALL). Normal human cells have 46 chromosomes, half from each parent, but hypodiploid ALL is characterized by fewer than 44 chromosomes. Chromosomes are highly condensed pieces of DNA, the molecule that carries the inherited instructions for assembling and sustaining a person. The research appears in the January 20 advance online edition of the scientific journal Nature Genetics.
The study, the largest ever focused on hypodiploid ALL, confirmed that this tumor has distinct subtypes distinguished by the number of chromosomes lost and the submicroscopic genetic alterations they harbor. Researchers found evidence suggesting more than one-third of patients with a subtype known as low hypodiploid ALL have Li-Fraumeni syndrome. Families with Li-Fraumeni syndrome harbor inherited mutations in the TP53 tumor suppressor gene and have a high risk of a range of cancers. Hypodiploid ALL had not previously been recognized as a common manifestation of Li-Fraumeni syndrome.
Researchers reported that the major hypodiploid subtypes are both sensitive to a family of compounds that block the proliferation of cancer cells. The compounds include drugs already used to treat other cancers. The subtypes are low hypodiploid ALL, characterized by 32 to 39 chromosomes, and near haploid ALL, which has 24 to 31 chromosomes.
“This study is a good example of the important insights that can be gained by studying the largest possible number of patients in as much detail as possible. This approach led us to key insights about these leukemia subtypes that we would otherwise have missed,” said the study’s senior and corresponding author, Charles Mullighan, MBBS(Hons), MSc, M.D., an associate member of the St. Jude Pathology Department. Mullighan is a Pew Scholar in Biomedical Sciences.
Science Brief thanks to EurekAlert.
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Genetic basis of high-risk childhood cancer points to possible new drug treatment strategy
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