WA team IDs leukaemia key

Researchers at the Western Australian Institute for Medical Research (WAIMR) have identified a key gene in acute myeloid leukaemia (AML) that could serve both as a prognostic marker and a target for new drugs to treat the disease.

WAIMR director Prof Peter Klinken said the MLF1 gene mediated the emergence of drug-resistant leukaemic cells after chemotherapy.

"We've been working for nearly two decades to identify genes involved in the development of leukaemia, and we've spent five years trying to work out what MLF1 is doing," Klinken said.

"We think that, in addition to wiping out most leukaemic cells, chemotherapy drugs also create new mutations, so the leukaemia appears in a new form.

"Through a process of selection, some of the surviving leukaemic cells carry mutations that make the cells resistant to the chemotherapy agent."

The WAIMR researchers believe MLF1 codes for a transcription regulator, and mutations that up-regulate the gene make cells more resistant to chemotherapy.

"We've found that MLF1 is mutated by chromosomal translocations, and is involved in specific forms of acute myeloid leukaemia," Klinken said. "If its expression levels in the leukaemic cells increase, it's associated with a poor prognosis."

Klinken said one aim was to develop a quantitative polymerase chain reaction screen to measure MLF1 expression levels in patients' AML cells, as a prognostic indicator.

"The paradigm is chronic myeloid leukaemia," he said. "The chromosomal translocation, called Philadelphia chromosome, was identified 30-40 years ago, and it was the first translocation to be linked to leukaemia.

"In the 1980s, [mutant] bcr-abl genes associated with the translocation were identified. Today we have Gleevec, a drug which is incredibly effective in treating chronic myeloid leukaemia, by inhibiting the mutant protein."

Klinken said a future drug for acute myeloid leukaemia would probably work by disrupting some component the transcription complex that activates the gene, or by directly disrupting the activity of the MLF1 protein.

AML is predominantly a disease of middle age. Klinken said with 650-odd new cases in Australia, every case of the highly aggressive leukaemia is very personal in its impact on patients and their families.