This family of blood cancers is known as myelodysplastic syndromes and are a difficult-to-treat type of blood disease that occur when blood cells in the bone marrow do not mature properly.

A scientific team at the Washington University School of Medicine (St. Louis, MO, USA) discovered the mutation in a gene known as small nuclear ribonucleic acid (RNA) auxiliary factor 1(U2AF1). They sequenced the entire genome of a 65-year old man with myelodysplastic syndrome that had progressed to leukemia and compared it with the genome of his tumor cells.

After identifying the U2AF1 mutation in three patients through whole-genome sequencing, the investigators scoured the gene for the mutation in another 150 patients with myelodysplastic syndromes. They identified the mutation in 13, or nearly 9% of the patients. The mutations were acquired during development of myelodysplastic syndromes because they were not present in normal cells obtained from each patient. Patients were almost three times as likely to develop leukemia if they had a mutation in the U2AF1 gene. The disorder progressed to leukemia in 15.2% of patients with the mutation, compared with 5.8% of those without the genetic anomaly.

Normally, the U2AF1 gene makes a protein involved in splicing RNA, a sister molecule of DNA that carries the instructions for building proteins. Splicing brings together different sections of RNA necessary to make a protein and discards those sections that are not needed. The mutated version of the gene still produces a protein, but its splicing activity is altered, which may be important for the development of some cancers.

Timothy Graubert, MD, an associate professor of medicine and senior author of the study said, "A mutation in any one of these eight genes occurs in up to 50% of patients with myelodysplastic syndromes. Because these changes are so common, we think there are likely to be implications for improving the diagnosis of the disorder and finding new therapeutic options." Myelodysplastic syndromes are hematopoietic stem cell disorders that often progress to chemotherapy-resistant secondary acute myeloid leukemia. About 28,000 Americans are diagnosed with the disorder each year, most of them over the age of 60. The study was published on December 11, 2011, in the journal Nature Genetics.

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