Researchers find genetic link to leukemias with an unknown origin

Feb 18, 2010
This is AML bone marrow showing immature leukemia cells. Credit: Abramson Cancer Center

Although leukemia is one of the best studied cancers, the cause of some types is still poorly understood. Now, a newly found mutation in acute myeloid leukemia patients could account for half of the remaining cases of adult acute leukemia with an unknown origin.

"The of leukemia has been studied for the last 20 years and we thought we had found most of the common genes for leukemia," comments senior author Craig B. Thompson, MD, director of the Abramson Cancer Center of the University of Pennsylvania. "Now we're able to point to a distinct type of mutation for half of the remaining leukemias for which we didn't know the cause and between one-quarter and one-third of leukemias in older patients." The findings are described online this week in Cancer Cell.

Using samples from a Penn tissue bank of (AML), Thompson and colleagues found that AML patients have increased levels of a molecule called 2HG. AML is a quick-moving, deadly cancer that starts in the bone marrow and soon moves into the blood. The increased amounts of 2HG stem from a mutation in one of two related metabolic enzymes, IDH1 or IDH2.

Screening for elevations in 2HG in the tissue bank, the team found that IDH1 and IDH2 mutations are observed in over 23 percent of the AML patients studied. A shared feature of cancer-related IDH mutations is increased production of 2HG.

What's more, the IDH gene mutations are the first known cancer mutations that result in the creation of a protein with a new . Most cancer-causing mutations make the mutated protein either overactive or inactive in performing its normal function. In contrast, the mutations in the IDH proteins give these enzymes the blueprint to create a new molecule not normally produced by cells. Interestingly, the researchers also found that IDH2 mutations are more common than IDH1 mutations in AML.

Other gene-related causes of leukemia include breaks and reformations in chromosomes called translocations.

The ease with which the researchers were able to detect IDH mutations in tumor samples, and the ability to identify patients with these mutations due to the presence of increased 2HG gives hope for better detection of AML and suggests that blocking the production of 2HG might reverse the ability of the mutant genes to maintain the leukemic cells.

"If we're able to block tumors from producing 2HG, perhaps we would be able to stop the patient's leukemia," states Thompson. Exactly why 2HG production leads to is not yet clear. It does not appear to act like other cancer-causing metabolites which induce further mutations. One possibility raised in the manuscript is that 2HG accumulation may block the ability of the leukemic cells to differentiate into normal blood cells.

Explore further: 20 years of data shows treatment technique improvement for advanced abdominal cancer

Related Stories

Metabolite common among cancers

Feb 08, 2010

A study published online on February 8 in the Journal of Experimental Medicine reports that several distinct mutations found in a subset of patients with acute myelogenous leukemia (AML) result in excess production of the ...

Gene mutation improves leukemia drug's effect

Jun 17, 2008

Gene mutations that make cells cancerous can sometimes also make them more sensitive to chemotherapy. A new study led by cancer researchers at Ohio State University shows that a mutation present in some cases of acute leukemia ...

Recommended for you

Unraveling the 'black ribbon' around lung cancer

1 hour ago

It's not uncommon these days to find a colored ribbon representing a disease. A pink ribbon is well known to signify breast cancer. But what color ribbon does one think of with lung cancer?

Survival hope for melanoma patients thanks to new vaccine

7 hours ago

(Medical Xpress)—University of Adelaide researchers have discovered that a new trial vaccine offers the most promising treatment to date for melanoma that has spread, with increased patient survival rates and improved ability ...

User comments : 0

More news stories

Classifying cognitive styles across disciplines

Educators have tried to boost learning by focusing on differences in learning styles. Management consultants tout the impact that different decision-making styles have on productivity. Various fields have ...

Internet use may cut retirees' depression

Spending time online has the potential to ward off depression among retirees, particularly among those who live alone, according to research published online in The Journals of Gerontology, Series B: Psychological Sciences an ...

Tiny power plants hold promise for nuclear energy

Small underground nuclear power plants that could be cheaper to build than their behemoth counterparts may herald the future for an energy industry under intense scrutiny since the Fukushima disaster, the ...