Children with Down syndrome are 10 to 20 times as likely as unaffected children to develop leukemia. They most commonly develop a type known as acute megakaryoblastic leukemia (AMKL), which is extremely rare in children without Down syndrome.

"This study, for the first time, defines a part of the molecular pathway leading to acute megakaryoblastic leukemia," said John Crispino, Ph.D., assistant professor in the Ben May Institute for Cancer Research at the University of Chicago and director of the study. "Having three copies of chromosome 21 places children with Down syndrome at increased risk for leukemia, then this abnormality tips the balance toward AMKL."

"This is a rare malignancy," added co-author Michelle Le Beau, Ph.D., professor of medicine at the University, "but a great deal of what we now know about the molecular basis of cancer has come from disorders like this. Our finding pinpoints a specific pathway that leads to this kind of cancer, offers a method for rapid and precise diagnosis, and suggests more focused ways to treat this disease."

Unlike most studies, which begin with a disease then search for the genetic trigger, this one began with a suspect gene. Crispino's laboratory had been interested in a gene called GATA1 for years because it played a role in the maturation of blood cells.

Dr. Crispino hypothesized that GATA1 might be mutated or dysregulated in leukemia. He contacted Le Beau, an expert on the genetics of leukemia. After they identified a patient with Down syndrome who had a mutation in GATA1 and had acute megakaryoblastic leukemia in a small pilot study they began searching for other patient
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Contact: John Easton
jeaston@uchospitals.edu
773-702-6241
University of Chicago Medical Center
11-Aug-2002