Genetic discovery will aid diagnosis of rare childhood cancer

St. Jude Children's Research Hospital (ALSAC)
Friday, 10 August 2001

May lead to new medical therapy

(Memphis, Tennessee, August 10, 2001) The discovery of the abnormal fusion of two gene segments will help scientists readily diagnose a rare form of childhood cancer and may help lead to a cure. Megakaryoblastic leukemia is a type of cancer that most frequently strikes toddlers and is approximately 75 percent fatal.

The report, published in the July issue of Nature Genetics, identifies RBM15-MKL1, a gene abnormally fused from segments of two previously unidentified genes. Stephan Morris, M.D., and Zhigui Ma, M.D., Ph.D., of Memphis' St. Jude Children's Research Hospital and Johann Hitzler, M.D., of Toronto's Hospital for Sick Children led the study.

The genetic abnormality is likely a factor in the onset of acute megakaryoblastic leukemia, a rare form of acute myeloid leukemia (AML).

Clinicians can currently use the new findings to easily diagnose megakaryoblastic leukemia. In addition, this discovery could lead to the development of a more effective, less toxic medical therapy for a cancer that is virtually untreatable. Only about one-quarter of the children with this type of AML respond to available treatments.

Megakaryoblastic leukemia strikes infants and toddlers up to age 4. About 20 percent of all childhood leukemias are of the AML type, of which roughly one-tenth are megakaryoblastic leukemias.

"Using this discovery in conjunction with DNA testing, clinicians can now rapidly and unequivocally determine whether a child has this rare form of AML within just one or two days," Morris said. "In addition, with this fusion gene now identified, the biomedical industry should be able to design medications specifically tailored to target the abnormal functions of the fused gene that lead to the development of these leukemias."

Scientists at both St. Jude and the Hospital for Sick Children located the two genes and identified the abnormality. Specific parts of these two normal genes break off and then come together to form the new, abnormal fusion gene, RBM15-MKL1, found uniquely in the acute megakaryoblastic leukemias. The normal genes, named by the scientists RNA-binding motif protein-15 (RBM15) and Megakaryoblastic Leukemia-1 (MKL1), are located respectively on chromosome number 1, the largest chromosome, and chromosome number 22, the smallest chromosome.

"This discovery was made possible through information available from the recently completed human genome map and the capabilities of our Hartwell Center for Bioinformatics and Biotechnology at St. Jude," Morris said.

St. Jude Children's Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). ALSAC covers all costs not covered by insurance for medical treatment rendered at St. Jude Children's Research Hospital. Families without insurance are never asked to pay.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org