Open Access Open Badges Research article

FLT3 mutation incidence and timing of origin in a population case series of pediatric leukemia

Patrick Chang123, Michelle Kang1, Anny Xiao1, Jeffrey Chang1, James Feusner2, Patricia Buffler4 and Joseph Wiemels1*

Author Affiliations

1 Department of Epidemiology and Biostatistics, UCSF, Helen Diller Cancer Research Building, 1450 3rd Street, San Francisco, CA 94158, USA

2 Children's Hospital and Research Center, Oakland, 747 52nd Street, Oakland, CA 94609, USA

3 Children's Center for Cancer and Blood Disorders of Northern Virginia, 6565 Arlington Blvd, Suite 200, Falls Church VA 22042, USA

4 School of Public Health, UC Berkeley, 1995 University Avenue, Suite 460, Berkeley, CA 94704, USA

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BMC Cancer 2010, 10:513  doi:10.1186/1471-2407-10-513

Published: 27 September 2010



Mutations in FLT3 result in activated tyrosine kinase activity, cell growth stimulation, and a poor prognosis among various subtypes of leukemia. The causes and timing of the mutations are not currently known. We evaluated the prevalence and timing of origin of FLT3 mutations in a population series of childhood leukemia patients from Northern California.


We screened and sequenced FLT3 mutations (point mutations and internal tandem duplications, ITDs) among 517 childhood leukemia patients, and assessed whether these mutations occurred before or after birth using sensitive "backtracking" methods.


We determined a mutation prevalence of 9 of 73 acute myeloid leukemias (AMLs, 12%) and 9 of 441 acute lymphocytic leukemias (ALLs, 2%). Among AMLs, FLT3 mutations were more common in older patients, and among ALLs, FLT3 mutations were more common in patients with high hyperdiploidy (3.7%) than those without this cytogenetic feature (1.4%). Five FLT3 ITDs, one deletion mutation, and 3 point mutations were assessed for their presence in neonatal Guthrie spots using sensitive real-time PCR techniques, and no patients were found to harbor FLT3 mutations at birth.


FLT3 mutations were not common in our population-based patient series in California, and patients who harbor FLT3 mutations most likely acquire them after they are born.