For the first time, a genetic link specific to the risk of
childhood leukaemia has been identified, according to a team of researchers from
Memorial Sloan-Kettering Cancer Center, St Jude Children's Research Hospital, University
of Washington, and other institutions. The discovery was reported online today
in the journal Nature Genetics.
"We're in unchartered territory," said study
author Kenneth Offit, MD, MPH, Chief of the Clinical Genetics Service at
Memorial Sloan-Kettering. "At the very least this discovery gives us a new
window into inherited causes of childhood leukaemia. More immediately, testing
for this mutation may allow affected families to prevent leukaemia in future
The mutation was first observed in a family treated at
Memorial Sloan-Kettering of which several family members of different
generations had been diagnosed with childhood acute lymphoblastic leukaemia
(ALL). A second, non-related, leukaemia-prone family cared for at a different
hospital was later found to have the same mutation. A series of experiments
were conducted confirming that the observed mutation compromised the normal
function of the gene, which may increase the risk of developing ALL.
The inherited genetic mutation is located in a gene called
PAX5, which is known to play a role in the development of some B cell cancers,
including ALL. PAX5, a transcription factor or "master gene",
regulates the activity of several other genes and is essential for maintaining
the identity and function of B cells. In all study participants, one of the two
copies of the PAX5 gene was missing, leaving only the mutated version. The
research continues as the researchers believe additional genetic factors played
a role in the development of ALL in these patients.
ALL is the most common form of cancer in children, with 3 000
children and young adults diagnosed each year in the United States.
Dr Offit hopes that ongoing research will also determine
what percentage of childhood ALL patients have the PAX5 mutation. Current
estimates suggest that it is rare. Additionally, the newly discovered gene
mutation may someday help scientists determine how to target transcription
factors to treat other non-inherited forms of leukaemia where the PAX5 mutation
"With a better understanding of the genetic elements
that induce cancer susceptibility, or drive cancer to grow, we can more
precisely target therapy as well as potentially prevent cancer from occurring
in the first place," added Dr Offit.
In 1996, a similar study of cancer-prone families allowed Dr
Offit and his team to identify the most common mutation of BRCA2, associated
with an increased risk of breast and ovarian cancer, and particularly common
among individuals of Ashkenazi Jewish ancestry.