New insight into most common type of infant leukaemia

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baby and globe_oncology news australiaPeter Mac researchers have made an important advance in our understanding of the most common sub-type of leukaemia in infants, providing a new lead that could fast-track development of a targeted and more effective treatment.

More than 80% of infants diagnosed with either Acute Myeloid Leukaemia (AML) or Acute Lymphoblastic Leukaemia (ALL), and up to 10% of adults, have a sub-type of these diseases known as MLL Translocated leukaemia. Prognosis is particularly poor for infants with 40-50% unlikely to survive.

Peter Mac’s Professor Mark Dawson has studied Acute Leukaemia and this particular sub-type for a decade and says these latest findings provide a step towards next-generation therapy for a disease where treatment has changed little since the 1970s and five-year survival rates in older adults following diagnosis remains less than 20%.

“Every other disease that I’ve treated in my time as a haematologist has had one, if not very many, new drugs come along to improve treatment but this has not been seen generally for leukaemia and for AML in particular it is none – zero,” Professor Dawson says.

“This is a disease where patients affected are often young and fit when first diagnosed but
do not respond to conventional therapy.” Professor Mark Dawson

Research by Professor Dawson’s team along with international collaborators has – for the first time – explained the role played by two proteins (BRD4 and DOT1L) which are known to be key regulators of MLL translocated leukaemia.

The targeted diseaseHis research identified a previously unknown cooperation between these proteins, showing how they depend on each other to progress the disease.

Drugs which target both of these proteins are now in separate clinical trials as potential leukaemia treatments. Professor Dawson’s research suggests a combination therapy involving drugs that target both proteins at the same time may be an effective strategy against the disease.

Professor Dawson’s findings explaining the interdependence of BRD4 and DOT1L in MLL leukaemia was published in the journal Nature Structural & Molecular Biology on Monday.

“We’ve always known that these leukaemias needed these regulators but what we didn’t know was why, and we didn’t know that they spoke to each other to drive the disease,” Professor Dawson says.

“The good news is we don’t have to develop new drugs in light of this research because they are already here and in clinical trials,” Professor Dawson says.

Co-lead authors on the paper are Dr Omer Gilan, a molecular biologist and biochemist, and bioinformatician Dr Enid Lam.

“These days you need this multi-factorial skillset, a multi-disciplinary team, to answer these big and difficult questions about hard to treat diseases ,” Professor Dawson also said.
[hr] Source: Peter Mac


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