Featured Research

from universities, journals, and other organizations

Genetic link to leukemias with an unknown origin discovered

Date:
February 19, 2010
Source:
University of Pennsylvania School of Medicine
Summary:
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.

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.

Related Articles


"The molecular biology 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 acute myeloid leukemia (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 enzymatic activity. 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 leukemia 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.

The research was funded in part by grants from the National Cancer Institute and the Abramson Family Cancer Research Institute.

Other co-authors in addition to Thompson include Patrick Ward, MD/PhD student, and Martin Carroll, MD, from the Abramson Cancer Center, and Ross Levine, MD, from the Memorial Sloan-Kettering Cancer Center, as well as researchers from Agios Pharmaceuticals and Princeton University. Thompson is co-founder and consultant to Agios.


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University of Pennsylvania School of Medicine. "Genetic link to leukemias with an unknown origin discovered." ScienceDaily. ScienceDaily, 19 February 2010. <www.sciencedaily.com/releases/2010/02/100218125158.htm>.
University of Pennsylvania School of Medicine. (2010, February 19). Genetic link to leukemias with an unknown origin discovered. ScienceDaily. Retrieved November 29, 2014 from www.sciencedaily.com/releases/2010/02/100218125158.htm
University of Pennsylvania School of Medicine. "Genetic link to leukemias with an unknown origin discovered." ScienceDaily. www.sciencedaily.com/releases/2010/02/100218125158.htm (accessed November 29, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Rural India's Low-Cost Sanitary Pad Revolution

Rural India's Low-Cost Sanitary Pad Revolution

AFP (Nov. 28, 2014) — One man hopes his invention -– a machine that produces cheap sanitary pads –- will help empower Indian women. Duration: 01:51 Video provided by AFP
Powered by NewsLook.com
Research on Bats Could Help Develop Drugs Against Ebola

Research on Bats Could Help Develop Drugs Against Ebola

AFP (Nov. 28, 2014) — In Africa's only biosafety level 4 laboratory, scientists have been carrying out experiments on bats to understand how virus like Ebola are being transmitted, and how some of them resist to it. Duration: 01:18 Video provided by AFP
Powered by NewsLook.com
WHO Says Male Ebola Survivors Should Abstain From Sex

WHO Says Male Ebola Survivors Should Abstain From Sex

Newsy (Nov. 28, 2014) — WHO cites four studies that say Ebola can still be detected in semen up to 82 days after the onset of symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins