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: Natural (born) killer cells battle pediatric leukemia

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

Biomarker in aggressive breast cancer identified

10 hours ago

Two Northwestern University scientists have identified a biomarker strongly associated with basal-like breast cancer, a highly aggressive carcinoma that is resistant to many types of chemotherapy. The biomarker, ...

MRI better detects recurrent breast cancer

11 hours ago

(HealthDay)—Single-screening breast magnetic resonance imaging (MRI) detects 18.1 additional cancers after negative findings with mammography and ultrasonography (US) per 1,000 women with a history of breast ...

Natural (born) killer cells battle pediatric leukemia

23 hours ago

Researchers at Children's Hospital Los Angeles have shown that a select team of immune-system cells from patients with leukemia can be multiplied in the lab, creating an army of natural killer cells that ...

User comments : 0