Family studies reveal leukemia gene

A genetic defect found on the GATA2 gene predisposes people to acute myeloid leukemia (AML) and myelodysplasia, researchers have learned. The genetic mutation was first discovered in a person in central Washington who had been successfully treated for leukemia in 1992 by means of a bone marrow transplant, and who had several family members with myelodysplastic syndrome, myeloid leukemia, and intractable mycobacteria infections.

Marshall S. Horwitz, MD, PhD, who practices genetic medicine at the University of Washington (UW) Medical Center and the UW Center for Human Development and Disability—both in Seattle—helped carry out the US portion of the study after learning of his patient's familial connection to the blood diseases. Colleagues in Australia had described a family with a similarly inherited blood disorder, and 18 years later, the international team hit upon the mutated gene responsible for the leukemia affecting both families. They have since identified abnormal GATA2 genes in more than 20 families and individual persons in the United States, Australia, and Canada.

In the first four families studied, several members over the course of generations had developed AML, with onset occurring from the teen years to the early 40s. Disease course was rapid.

As the investigators noted in Nature Genetics, identifying such predisposing genes as GATA2 to familial forms of AML and myelodsyplastic syndrome is critical for more effective diagnosis and prognosis of the diseases, as well as selection of related bone marrow transplant donors and development of therapeutic agents.

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