21 Jan 2013, BioSpectrum Bureau , BioSpectrum
Singapore: Researchers at the St Jude Children's Research Hospital, US, have found the first evidence of the genetic basis for this high-risk leukemia, which is known as hypodiploid acute lymphoblastic leukemia (ALL).
The study identified a possible lead in the treatment of two childhood leukemia subtypes known for their dramatic loss of chromosomes and poor treatment outcomes. Normal human cells have 46 chromosomes, half from each parent, but hypodiploid ALL is characterized by fewer than 44 chromosomes. The research has been published in the January 20 advance online edition of Nature Genetics.
The study, which is 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 previously not 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, Dr Charles Mullighan, who is also Mullighan Pew Scholar in biomedical sciences.and an associate member of the St Jude Pathology Department.
"The cure rate for hypodiploid ALL is only about half that obtained overall for children with ALL. The findings of this study are very important and have the potential to impact how this high-risk subset of childhood ALL is treated," said Dr Stephen Hunger, chair of the Children's Oncology Group ALL committee and one of the paper's co-authors.
He added, "This study grew out of the efforts of Hank Schueler, a teenager who died from hypodiploid ALL. He wanted to find ways to help treat other children with this type of leukemia. After he passed away, his parents established a foundation to support research in hypodiploid ALL. We thought that one way to do this was to conduct the genomic analyses reported in this paper. These findings would not have been possible without Hank's idea and without support from the Schueler family."