Peter Mac researchers have made another important discovery in Acute Myeloid Leukaemia (AML), showing how a protein needed for healthy cell replication is suppressed by the cancer.

The research describes how a gene fusion protein called MLL-AF9 suppresses expression of the Id2 protein as part of the leukaemia-forming process and, importantly, when Id2 levels are restored the cancer’s growth was impaired.

It suggests a drug that influences Id2 levels could be an effective strategy against a disease which has seen little in the way of new treatments in decades.

Existing AML treatment require the patient to undergo a bone marrow transplant, which poses additional risk of graft rejection and they effectively lose their immune system in the process.

“There is a particularly urgent need for new targeted, drug-based therapies for AML, and with every discovery of what’s driving the cancer we take a step closer to achieving that,” says Professor Ricky Johnstone who led the research.

“What we found in this case was the suppression of Id2 protein plays an important, and previously unrecognised, role in allowing MLL re-arranged AML cancer cells to take hold and spread.

“Drugs that influence levels of this protein, or stop it being suppressed by the cancer, could provide a much-needed new avenue to combatting this disease.”

The research paper, titled Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL Re-Arranged Acute Myeloid Leukaemia was published overnight in the journal Cancer Cell.

More than 70% of infants diagnosed with AML, and up to 10% of adults, have this MLL sub-type of the disease.

Prof Johnstone says the link between Id2 protein and MLL AML was also seen in another sub-type of the cancer – known as t(8;21) AML – suggesting the findings, and any new treatment based on this, may have broader application.

The discovery comes after the publication in June of Peter Mac-led research which described, for the first time, the co-dependent roles of two other proteins - BRD4 and DOT1L - in driving MLL AML.

Drugs targeting these proteins are already in independent clinical trials and this research suggests these drugs could work better in combination.

What is AML?

Acute myeloid leukemia (AML) is a cancer affecting the myeloid line of blood cells. It is characterised by the rapid growth of abnormal white blood cells which accumulate in the bone marrow and interfere with the production of normal blood cells. More than 1000 Australians are diagnosed with AML per year, and less than 25% survive more than five-years from diagnosis.1

1 https://canceraustralia.gov.au/affected-cancer/cancer-types/leukaemia/acute-myeloid-leukaemia-statistics