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Acute myeloid leukemia is a type of cancer where the bone marrow makes abnormal myeloblasts, a type of white blood cell. Medtech THAI STUDIO LAB 249/

Acute myeloid leukaemia: researchers zero in on treatment options for aggressive blood cancer

Just three days after being diagnosed with acute myeloid leukaemia (AML), the wife of Sky Sports presenter Simon Thomas tragically died. Gemma Thomas was one of more than 3,000 people diagnosed with AML in the UK in the last year.

AML is the commonest aggressive adult human blood cancer. Despite advances in our understanding of the disease, we need to do more research to increase the number of patients who are cured.

Every day we need to make new blood cells to stay alive. These blood cells are made in the bone marrow and carry oxygen that gives us energy, fight infection and stop bleeding.

AML is a cancer of the bone marrow that results in failure to produce the new blood cells we need. People with the disease tend to get easily fatigued, develop infections, or bruise or bleed without any obvious reason. In some people the infection or bleeding may cause life-threatening illness.

People with AML often become unwell very suddenly, even though the disease may have been present for a while.

Many patients need emergency treatment with chemotherapy. The treatment aims to kill AML cancer cells in the bone marrow. Other treatments include blood transfusions and antibiotics. Death during this early stage of treatment, as in the case of Gemma Thomas, is a tragic but rare complication.

After initial treatment, patients need further courses of chemotherapy and, in some cases, a blood stem cell transplant. Although this aims to cure the disease, it is not always successful. Because of the intense side effects of this treatment, only medically fit patients are able to have it. For other patients, gentler treatment is used – treatment that aims to keep the AML at bay but will not get rid of the disease.

New treatments

The cause of AML is unknown in most patients, but there are known risk factors such as existing blood disorders, prior chemotherapy and exposure to radiation. (Chemotherapy and radiation can interfere with the DNA of healthy cells.)

Research into AML is essential to improve outcomes. In order to develop new treatments, we need to understand what is happening in the cancer cells. When leukaemia develops, bone marrow cells start to divide rapidly and fail to mature into normal blood cells.

We now know that this results from sequential genetic damage (mutations) in these immature leukaemia cells. These genetic changes are not usually inherited and are not passed down to children. The genetic changes are acquired during a patient’s lifetime and occur only in blood cells. Investigating how these mutations lead to AML forms the basis for several new cancer therapies that are being trialled in Oxford.

One such target is the IDH2 gene, which is mutated in around one-third of AML patients. This leads to a block in blood cell maturation. A drug directed against mutant IDH2 has been approved in the US for the treatment of suitable individuals. Research in the MRC Molecular Haematology Unit in Oxford has demonstrated that the drug restores the ability of the bone marrow to make blood.

Another treatment option explores the fact that leukaemia cells are able to evade the immune system, which in healthy people recognises and removes abnormal cells. Leukaemia cells evade this protective mechanism by producing a don’t-eat-me signal, called CD47. The haematology unit in Oxford is leading a second trial into a new drug that hides this signal. It is hoped that this will allow the body’s own immune cells to target and destroy AML.

With the development of new scientific techniques, international collaborations and clinical trials, treatment options for AML are likely to increase in future years. We hope that this will translate into improved prognosis and quality of life for patients with this devastating disease.

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