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.