A mutation in the PAX5 gene has been identified for the first time as the genetic cause for acute lymphoblastic leukemia (ALL). The research carried out by a team of researchers from Memorial Sloan-Kettering Cancer, St. Jude children’s research Hospital and University of Washington published in the journal Nature Genetics is the first time that the specific genetic cause has been attributed to the disease.
ALL is the most common form of childhood cancer, with approximately 3,000 children and young adults being diagnosed each year in the United States.
“We’re in uncharted 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 leukemia. More immediately, testing for this mutation may allow affected families to prevent leukemia in future generations.”
The PAX5 genetic mutation plays a role in the development of some B cell cancers including ALL. PAX5 acts as a transcription factor or “master gene,” regulating 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.
“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.
Sohela Shah, Kasmintan A Schrader, Esmé Waanders, Andrew E Timms, Joseph Vijai, Cornelius Miething, Jeremy Wechsler, Jun Yang, James Hayes, Robert J Klein, Jinghui Zhang, Lei Wei, Gang Wu, Michael Rusch, Panduka Nagahawatte, Jing Ma, Shann-Ching Chen, Guangchun Song, Jinjun Cheng, Paul Meyers, Deepa Bhojwani, Suresh Jhanwar, Peter Maslak, Martin Fleisher, Jason Littman, Lily Offit, Rohini Rau-Murthy, Megan Harlan Fleischut, Marina Corines, Rajmohan Murali, Xiaoni Gao, Christopher Manschreck, Thomas Kitzing, Vundavalli V Murty, Susana C Raimondi, Roland P Kuiper, Annet Simons, Joshua D Schiffman, Kenan Onel, Sharon E Plon, David A Wheeler, Deborah Ritter, David S Ziegler, Kathy Tucker, Rosemary Sutton, Georgia Chenevix-Trench, Jun Li, David G Huntsman, Samantha Hansford, Janine Senz, Tom Walsh, Ming Lee, Christopher N Hahn, Kathryn G Roberts, Mary-Claire King, Sarah M Lo, Ross L Levine, Agnes Viale, Nicholas D Socci, Katherine L Nathanson, Hamish S Scott, Mark Daly, Steven M Lipkin, Scott W Lowe, James R Downing, David Altshuler, John T Sandlund, Marshall S Horwitz, Charles G Mullighan, Kenneth Offit. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. Nature Genetics, 2013; DOI: 10.1038/ng.2754