Scientists identify early gene changes that precede blood cancer

Date: Dec-01-2014 Using DNA samples from research unrelated to cancer, two teams of scientists

have uncovered early, pre-cancerous genetic changes in the blood that are linked to

increased chances of developing blood cancers such as leukemia, lymphoma or

myelodysplastic syndrome.

Scientists have

identified some early gene mutations - believed to start in blood stem cells - that

are linked to increased risk of blood cancers like leukemia and lymphoma.

The teams believe their findings open new avenues for research into early

detection and prevention of blood cancer.

The studies - by teams from Harvard Medical School, the Harvard Stem Cell Institute

(HSCI), the Broad Institute of MIT and Harvard, and Harvard-affiliated hospitals - are

reported in two papers published in the New England Journal of Medicine.

Working independently of each other, the two groups of scientists uncovered a

detectable, pre-cancerous state in the blood that features mutations that develop in

a small number of genes known to be related to blood cancers.

The scientists think the mutations - which cells acquire over time - originate in

blood stem cells.

Steven McCarroll, senior author of one of the papers and assistant professor of

genetics at Harvard Medical School, says:

"People often think about disease in black and white - that there's 'healthy' and

there's 'disease' - but in reality most disease develops gradually over months or

years. These findings give us a window on these early stages in the development of

blood cancer."

Studies looked for early mutations in healthy people's blood

The studies are unusual because they tackled the research from an unconventional

direction. Most genetic research on cancer focuses on genomes of advanced cancers to

find mutated genes.

But in these two new studies, the teams looked at somatic mutations -

the copying mistakes in DNA that accumulate over time as cells divide and replicate -

in DNA from blood samples of people who did not have cancer or blood disorders.

They found that a subset - some, but not all - of mutations known to feature in

blood cancers were present in individuals who were 10 times more likely to develop

blood cancer later in life, compared with individuals who did not have these

mutations.

This cluster of pre-cancerous mutations - which is easily detected by DNA

sequencing - is rarely found in the blood of people under the age of 40. It becomes

more common with age and appears in more than 10% of people over the age of 70.

The scientists believe the mutations originate in blood stem cells, spurring mutated cells and their descendant clones to grow faster until they account for a

larger proportion of the cells in a person's blood.

They also suspect the early mutations wait for - and team up with - later

mutations to drive the cells toward cancer.

Most of the mutations occurred in just three genes: DNMT3A, TET2 and ASXL1.

Findings open new ways to research blood cancers, identify high-risk groups

Both teams were keen to point out that there would be no benefit in testing for

this pre-cancerous state - and there are no treatments available to address the

condition - in healthy people.

However, they suggest the findings open new ways to research blood cancer that

could lead to earlier detection and even prevention.

Prof. McCarroll, who is also director of genetics at the Broad's Stanley Center

for Psychiatric Research, says:

"The results demonstrate a way to identify high-risk cohorts - people who are at

much higher than average risk of progressing to cancer - which could be a population

for clinical trials of future prevention strategies. The abundance of these mutated

cells could also serve as a biomarker - like LDL cholesterol is for cardiovascular

disease - to test the effects of potential prevention therapies in clinical

trials."

Every 3 minutes in the US, a person is diagnosed with blood cancer, new cases of

which are expected to account for over 9% of all new cancer cases in 2014, according

to the Leukemia and Lymphoma Society.

In September 2014, Medical News Today learned of a study that uncovered

a
genetic network that drives an aggressive form of leukemia and its precursor -

myelodysplastic syndrome - paving the way for new treatments.

Written by Catharine Paddock PhD

Not to be reproduced without permission.

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Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.