Genetic Cause of Childhood Leukemia Identified

A genetic link to the risk of childhood acute lymphoblastic leukemia (ALL) has been identified and testing for this mutation may allow affected families to prevent leukemia in future generations.

A series of molecular tests, including exome sequencing and single nucleotide polymorphism arrays, have been conducted to confirm that the observed mutation compromised the normal function of the gene, but which may increase the risk of developing ALL.


Scientists at the Memorial Sloan-Kettering Cancer Center (New York, NY, USA) and other institutions first observed the mutation in a family treated at Memorial Sloan-Kettering of which several family members of different generations had been diagnosed with childhood ALL. A second, nonrelated, leukemia-prone family cared for at a different hospital was later found to have the same mutation.

The inherited genetic mutation is located in a gene called paired box gene 5 (PAX5) and also known as B-cell lineage specific activator protein (BSAP), which is known to play a role in the development of some B cell cancers, including ALL. PAX5 is a transcription factor or "master gene," that 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. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13.

The authors of the study hope that ongoing studies 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 noninherited forms of leukemia where the PAX5 mutation is present. ALL is the most common form of cancer in children, with 3,000 children and young adults being diagnosed each year in the USA.

Kenneth Offit, MD, MPH, a senior author of the study 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. 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.” The study was published on August 9, 2013, in the journal Nature Genetics.

Related Links:
Memorial Sloan-Kettering Cancer Center