Researchers have identified a genetic mutation linked to specific risk of childhood acute lymphoblastic leukemia (ALL), according to a research letter in the October issue of Nature Genetics (2013:45;1226-1231).
“These results represent a new syndrome of cancer susceptibility, which oncologists treating these children will need to keep in mind,” Kenneth Offit, MD, MPH, Chief of the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center and the paper's senior author, noted via email.
The team of researchers from Memorial Sloan-Kettering Cancer Center, St. Jude Children's Research Hospital, the University of Washington, and other institutions determined that a mutation in the PAX5 gene was present in several members of two unrelated families, all diagnosed with childhood ALL. PAX5 (known to play a role in the development of some B-cell cancers, including ALL) is a transcription factor that regulates the activity of several other genes essential to maintain the identity and function of B cells.
The researchers (first author is Sohela Shah, PhD, a research fellow in the Offit lab) also found that the mutation was present in two additional cases of ALL. And, further tests confirmed that the specific mutation compromised the normal genetic functioning of PAX5, which appeared to increase the risk of developing ALL.
The authors also note that although the data strongly implicate the PAX5 mutation as being linked to B-cell ALL susceptibility, study of additional cases is required to define the full spectrum of germline variations contributing to ALL pathogenesis.
“We're in unchartered territory,” Offit said. “At the very least this discovery gives us a new window into inherited causes of childhood leukemia. More immediately, testing for this mutation may allow affected families to prevent leukemia in future generations.”