Gene defect that may cause leukaemia discovered

Scientists have discovered a new genetic mutation which they say could identify people who are susceptible to acute myeloid leukaemia, a type of blood cancer that kills thousands every year.

An international team of researchers found mutations in a gene, called GATA2, which among other roles, controls the process that changes primitive blood-forming cells into white blood cells.

The findings, published in the journal Nature Genetics, could lead to a genetic test allowing people with a family history of leukaemia to find out if they carry the faulty gene before their symptoms emerge, the researchers said.

“While several genes have been discovered and linked to solid, malignant tumours such as breast cancer in families susceptible to those types of cancer, so far very few inherited mutations have been uncovered for blood cancers,” said Dr. Marshall Horwitz, of the University of Washington and lead researcher of the study.

The researchers started by studying four families who, over generations, have had several relatives with acute myeloid leukaemia. Their disease onset occurred from the teens to the early 40s.

The genetic mutation was first discovered in a patient from central Washington who was treated for leukaemia in 1992.

At that time, Horwitz decided to seek a possible genetic reason after learning his patient had several family members with myelodysplastic syndrome, myeloid leukaemia and intractable mycobacteria infections.

Myelodysplastic syndrome is a difficulty in producing certain kinds of blood cells.

After 18 years of research, the team finally hit upon the mutated gene responsible for the leukaemia that affect these families. They have gone on to identify abnormal GATA2 genes in more than 20 families and individuals.

“It’s likely that this inherited error is more common than we had thought,” the researchers noted.

In some families with a GATA2 mutation, the over-riding concern has been leukaemia, while others suffer dangerous infections from bacteria, viruses and fungi because of a lack of white blood cells to fight off germs.

Comparable GATA2 mutations also have been found in people with the more common, non-inherited leukaemias.

Previously, scientists linked mutations in 2 other genes, RUNX1 and CEBPA, to inherited forms of myelodysplastic syndrome and acute myeloid leukaemia. These genes bind to DNA and control the copying of information encoded in this molecule.

According to Horwitz, the GATA2 mutations in DNA occur adjacent to an amino acid mutated in some patients with terminal chronic myeloid leukaemia. This proximity suggests a common pathway may be critical for several types of myeloid malignancies, he said.

People at risk because of their pedigree eventually may obtain tests to detect this genetic error before symptoms emerge, the researchers said.

Learning that they have the gene mutation might help patients and their doctors decide on appropriate follow-up for early diagnosis and treatment of problems that might arise, they added.