Pathway Discovered that Sheds Light on Resistance in Acute Leukemias

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Discovery Major Step Forward In Treating Leukemia

ScienceDaily (Jan. 20, 2008) — Researchers at the University of East

Anglia have discovered for the first time a pathway that makes

cancerous leukaemia cells resistant to treatment.

The scientists found that death-resistant Acute Myeloid Leukaemia

cells are given their resistance by a genetic anti-oxidant pathway

called hemeoxygenase-1 or HO-1. This resistance pathway leads to

relapse of the disease and non-responsiveness to treatments. When this

pathway is inhibited, the cells lose their resistance and become

responsive to death-inducing agents.

The discovery is the first stage in the development of new drugs that

could significantly improve survival rates for leukaemia sufferers.

" This is a major step forward in the treatment of leukaemia and other

cancers, " said Prof MacEwan who led the research team.

" The next step will be a programme to develop a new set of targeted

therapies to treat not only Acute Myeloid Leukaemia, but other

leukaemias and other cancers. "

Leukaemia is one of the six biggest cancer killers in the UK and more

people die of Acute Myeloid Leukaemia (AML) than any other form of

leukaemia. AML attacks the white blood cells and is a common form in

both children and adults with leukaemia. It is currently treated by a

range of chemotherapy drugs. Many patients go on to have bone marrow

transplants due to commonly developing drug-resistance to their

initial chemotherapy.

The antioxidant response element (ARE) genes which include HO-1,

protect cells from damage and their killing off by cytotoxic agents

such as chemotherapy drugs. The team found that drug-resistant

leukaemia cells have overactive ARE genes that cause them to be

completely resistant to cytotoxic drugs, and that blocking this

pathway reverts the cells into responding normally to cytotoxic agents.

This research is published online in the journal Blood on January 18.

Adapted from materials provided by University of East Anglia.

University of East Anglia (2008, January 20). Discovery Major Step

Forward In Treating Leukemia. ScienceDaily. Retrieved January 20,

2008, from http://www.sciencedaily.com­

/releases/2008/01/080118093616.htm