Broken cell 'stopwatch' could lead to blood test to signal how fast leukaemia will progress

Thursday 10 June 2010

Cancer Research UK Press Release

Scientists have pinpointed key changes to the telomeres in the cells of leukaemia patients which could play a crucial role in the earliest stages of the disease, according to research published online in the journal Blood.

The research, funded by Cancer Research UK and Leukaemia & Lymphoma Research, used pioneering techniques for measuring the length of tiny structures known as telomeres – repeating sections of DNA which protect the ends of chromosomes during cell division.

Each time a cell divides the telomeres get shorter, limiting the cell’s lifespan.

But some cancer cells manage to bypass this safety check, allowing them to divide uncontrollably until the telomeres become so short they leave the chromosome ends completely exposed.

This makes them prone to fusing together causing instability and large-scale DNA mutations that can speed up cancer progression.

The discovery raises the prospect of developing a test to predict how quickly the telomeres are degrading which in turn would signal how fast the leukaemia was progressing.

It could also be a marker to help diagnose the disease earlier.

Dr Duncan Baird, lead author from Cardiff University, said: “This is the first time we’ve been able to directly show that shortened telomeres could trigger the progression of cancer.

“Our research shows that telomere length could act as a kind of stopwatch to predict how fast the disease might progress in cancer patients.

“Being able to detect key changes in the cell that trigger the progression of leukaemia is exciting – it could one day lead to a blood test to predict how aggressive a patient’s cancer is, helping doctors decide on the best treatment option.

“We’re now looking to see if telomeres fusing together may be a driving force in the progression of other types of cancer, such as bowel cancer.”

The researchers looked at blood samples from 41 chronic lymphocytic leukaemia (CLL) patients at different stages of the disease. They extracted chromosomes from the blood of these patients and measured the length of their telomeres.

The results showed that the cancer cells of patients at the most advanced stages of disease were more likely to have fused telomeres, suggesting that such events play a major role in the progression of the disease in these patients.

Dr David Grant, scientific director at Leukaemia & Lymphoma Research, said: “The discovery that blood cancer cells multiply uncontrollably because of permanent damage to their telomeres is extremely significant. This finding could lead to new ideas on how to deal with the serious genetic damage that promotes cancer growth and the design of new drugs to target the problem.”

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “This discovery is incredibly exciting, especially if it can also be used to monitor disease progression in other types of cancer cell.

“Understanding the key events that trigger cancer in cells is crucial as it opens up the door for new drug targets for slowing the progression of the disease.”

ENDS

For media enquiries please call the Cancer Research UK press office on 020 7061 8300 or the out of hours' duty press officer on 07050 264059.

Send to Email Address Your Name Your Email Address Evaluate the following expression to continue:
=  

  Cancel

NICE approves rituximab for chronic lymphocytic leukaemia

Friday 24 July 2009

Patients with chronic lymphocytic leukaemia (CLL), the most common form of adult leukaemia, will now be able to obtain the drug rituximab (MabThera) on the NHS after the National Institute of Health and Clinical Excellence (NICE) issued its final guidance on the therapy.

NICE has decided that rituximab should be made available as a first-line treatment, but only if used in combination with fludarabine and cyclophosphamide chemotherapy.

Rituximab is a type of biological therapy called a monoclonal antibody, which targets a protein on the surface of leukaemia cells.

The antibody attaches to these proteins so that the body's immune system recognises the need to destroy the cells.

Clinical trials of rituximab have shown that it can stop the disease from progressing for 10.5 months longer than chemotherapy alone, typically increasing progression-free survival from 2.7 years to 3.5 years.

It was also found to double the number of CLL patients who achieved complete remission compared with chemotherapy alone (36 per cent compared with 17 per cent).

Commenting on the decision to approve rituximab, Dr Carole Longson, director of the institute's Health Technology Evaluation Centre, said that the guidance "increases the treatment options available to people with this condition, wherever they live in England and Wales".

"After looking at all of the available evidence, the independent appraisal committee concluded that rituximab, when used as a first-line treatment for people with chronic lymphocytic leukaemia who are able to take fludarabine in combination with cyclophosphamide, represented an effective use of NHS resources," she explained.

Professor John Gribben, consultant haematologist and medical oncologist at Barts and the London NHS Trust, said that the NICE guidance is "great news" for both patients and clinicians as the therapy provides "significant benefits compared to chemotherapy alone".

He revealed: "The ability to add rituximab to chemotherapy is a major advance in the way we can treat chronic lymphocytic leukaemia.

"Where previously our goal was just to improve symptoms, for the first time we now have a treatment combination that is capable of producing much higher remission rates and more durable responses."

Professor Peter Johnson, Cancer Research UK's chief clinician, said: "Rituximab has already had a big impact on the chances of survival for patients with lymphoma. This new announcement is further good news for patients with chronic lymphocytic leukaemia.

"The development of this drug is an excellent example of how quality scientific research continues helping us to make progress in developing new drugs."

Send to Email Address Your Name Your Email Address Evaluate the following expression to continue:
=  

  Cancel

Lymphoma drug could treat leukaemia patients too

Monday 8 December 2008

A drug that is currently licensed to treat patients with non-Hodgkin lymphoma may also improve treatment for people with chronic lymphocytic leukaemia (CLL), according to new data.

Two separate studies were presented today (December 8th) at the American Society of Haematology annual meeting in San Francisco which suggest that rituximab (MabThera) can be effective against the most common form of leukaemia when combined with chemotherapy.

The first study, known as CLL-8, involved 817 previously untreated CLL patients. Those who were treated with chemotherapy plus rituximab had twice the likelihood of achieving complete remission compared to those treated with chemotherapy alone.

Only 27 per cent of patients receiving chemotherapy achieved complete remission, compared with 52 per cent of patients who were treated with chemotherapy and rituximab.

The second study, REACH, involved 552 relapsed CLL patients. It found that the combination of chemotherapy and rituximab stopped the disease in its tracks for an additional ten months on average when compared with chemotherapy alone.

Complete remission - the absence of any detectable signs of disease - was also nearly doubled among patients taking the combination, from 13 per cent to 24 per cent.

Professor Andrew Pettitt, consultant haematologist at Royal Liverpool University Hospital and a UK investigator on the second study, said: "These results represent a significant advance. The goals of treatment are to shrink the disease to the point where we cannot detect it and to maximise the length of time before the cancer returns."

Ed Yong, Cancer Research UK's health information manager, revealed: "Rituximab works by 'labelling' cancer cells so that the immune system can find and destroy them.

"It is currently approved in the UK to treat some types of lymphoma and the initial results from these trials suggest that it could help treat leukaemia too."

Mr Yong noted that the drug's manufacturers have applied for an EU licence so that rituximab can be used to treat leukaemia. If approved, the drug would then have to be recommended by the National Institute for Health and Clinical Excellence (NICE) before becoming available on the NHS.

He added: "We hope that this review process will be completed as swiftly as possible."

Please help us improve our news stories by taking our short survey

Send to Email Address Your Name Your Email Address Evaluate the following expression to continue:
=  

  Cancel

Scientists make leukaemia treatment advance

Monday 23 June 2008

UK researchers have developed an experimental drug that appears to be up to ten times more effective at killing leukaemia cells than existing treatments.

The drug, which was developed by a team at Newcastle University, is designed to treat patients with chronic lymphocytic leukaemia, many of whom become resistant to current treatments.

Drugs for chronic lymphocytic leukaemia work by inducing DNA damage. However, according to Dr Elaine Willmore, a researcher at the Northern Institute for Cancer Research, in some patients, leukaemia cells manage to repair the DNA and survive by employing an enzyme called DNA-PK.

The new drug, NU7441, is designed to target this enzyme and prevent it from repairing drug-induced DNA damage.

Dr Willmore explained: "Our results show that DNA-PK is present at high levels in chronic lymphocytic leukaemia cells from patients with a poor prognosis.

"Chemists at Newcastle University working together with KuDOS pharmaceuticals have designed a new drug called NU7441 that inhibits DNA-PK and stops it from mending broken DNA.

"When NU7441 is combined with drugs used for chronic lymphocytic leukaemia treatment it makes more tumour cells die and 're-sensitises' patients to their chemotherapy."

Laboratory research on NU7441 has shown that it could have a significant impact in patients who have developed resistance to their leukaemia treatment.

"Our exciting results show that in the laboratory, NU7441 'sensitises' the leukaemia cells to routinely used anti-cancer drugs, killing up to ten times more tumour cells - even in cells taken from patients who were very drug-resistant," Dr Willmore revealed.

The study, which was funded by the charity Leukaemia Research, is published in the journal Clinical Cancer Research and the charity's scientific director Dr David Grant described the findings as "incredibly exciting".

"Drugs like NU7441 will help combat chemotherapy resistance in those patients who really need more effective treatment for a form of leukaemia which is diagnosed in 3,500 patients in the UK every year," he said.

Send to Email Address Your Name Your Email Address Evaluate the following expression to continue:
=  

  Cancel