Navigation Links
Genome-wide mouse study yields link to human leukemia

Thanks to a handful of very special mice, scientists have discovered a new tumor suppressor gene and a unique chemical signature implicated in the development of human leukemia, findings that open up a "treasure box" of opportunity and possibility, study authors say.

Researchers in The Ohio State University Comprehensive Cancer Center bred a type of mouse that develops acute lymphoblastic leukemia (ALL). The mouse first goes through a pre-leukemic stage marked by rapidly expanding T cells and natural killer cells, both major components of the immune system.

In comparing the mice in the pre-leukemic stage and those with ALL with normal mice, researchers found that methylation, a chemical process that adds methyl molecules to DNA, silenced a number of genes ?but only in the mice with full-blown ALL.

Further tests revealed that the methylation pattern in the mice with leukemia is strikingly similar to the pattern of methylation in human leukemia.

In the process, the researchers also identified a new gene that when methylated, appears to interrupt normal cell death, a process called apoptosis.

"It's given us a whole new way to look at and possibly treat leukemia," says Michael Caligiuri, director of the OSU Comprehensive Cancer Center (OSUCCC) and senior co-author of the study. "It's also validated our mouse model as a good predictor of what happens in the development of human disease," he added.

The findings appear in Nature Genetics online at

"This is the first time anyone has examined methylation in leukemia on a genome-wide basis in a mouse, and the findings offer important implications for patient care, since we know that methylation, which alters gene function, can be reversed," says Christoph Plass, senior co-author and a member of the OSUCCC's Molecular Biology and Cancer Genetics and Experimental Therapeutics Programs.

While it was Caligiuri's laboratory that designed the mouse model, it was Plass who supervised the methylation studies. He and his colleagues used a system called Restriction Landmark Genome Sequencing (RLGS) to compare methylation patterns among the three groups of mice ?a method of using enzymes and gel electrophoresis to map tiny bits of DNA on a grid. The stretches of DNA, referred to as fragments, show up as smudgy blobs on a test film. If a fragment is dark and definite, it is not methylated. If, on the other hand, it loses at least 30 percent of its intensity, it is regarded as methylated.

In the study, the research team tested 2447 fragments in each animal. They found anywhere from 45 to 209 (.8 percent to 8.5 percent) of the fragments methylated in the mice with cancer, but only one or two methylated fragments in the other mice.

"Interestingly, that same range of methylated fragments is exactly what we find in human leukemia, too," says Caligiuri, "so that gives added merit to our mouse model as an investigative tool."

Using data from the methylation studies, Caligiuri and Plass were able to identify a particular stretch of DNA, called Id4, as a tumor suppressor gene.

Tumor suppressor genes help control cancer by identifying and getting rid of defective cells before they have a chance to mature and divide. When tumor suppressor genes lose that ability ?as they can if they are silenced through methylation or some other process, it gives cancer a chance to establish a foothold and spread.

Caligiuri says much more work needs to be done, but adds that the identification of Id4 as a likely tumor suppressor gene gives clinicians another possible target for intervention.

"We already have a drug, decitabine, that we know can reverse the effects of methylation," says Plass. "We are just beginning to figure out how it best works in humans, but simply knowing that we have a new target that may be meaningful in treating leukemia is a big step in the right direction."

Grants from the National Cancer Institute and the Leukemia and Lymphoma Society supported the research.

Additional co-authors from Ohio State include Li Yu, Chunhui Liu, Jeff Vandeusen, Brian Becknell, Zunyun Dai, Yue-Zhong Wu, Aparna Raval, Te-Hui Liu, Wei Ding, Charlene Mao, Shujun Liu, Laura Smith, Stephen Lee, Guido Marcucci and John Byrd. Laura Rassenti, from the University of California , San Diego , also contributed to the project.


Source:Ohio State University

Related biology news :

1. Man and mouse share genome structures
2. Report that delayed motherhood decreases life expectancy of mouse offspring
3. Agilent Technologies introduces advanced zebrafish, mouse microarrays for stem cell and developmental biology research
4. Stem cells in bone marrow replenish mouse ovaries
5. Mosaic mouse technique offers a powerful new tool to study diseases and genetics
6. Researchers extend mouse lifespan by protecting against free radicals
7. Gene therapy advance treats hemophilia in mouse models
8. Targeting a key enzyme with gene therapy reversed course of Alzheimers disease in mouse models
9. New technique could alter field of mouse genetics
10. Building a better mouse model of lung cancer: FHIT counts
11. Chemical compound inhibits tumor growth, size in new mouse study
Post Your Comments:

(Date:10/29/2015)... Oct. 29, 2015 Daon, a global leader ... has released a new version of its IdentityX ... North America have already installed IdentityX ... includes a FIDO UAF certified server component ... to activate FIDO features. These customers include some of ...
(Date:10/27/2015)... YORK , Oct. 27, 2015 In ... major issues of concern for various industry verticals such ... is due to the growing demand for secure & ... in various ,sectors, such as hacking of bank accounts, ... for electronic equipment such as PC,s, laptops, and smartphones ...
(Date:10/26/2015)... 2015  Delta ID Inc., a company focused on ... PC devices, announced its ActiveIRIS® technology powers the iris ... launched by NTT DOCOMO, INC in Japan ... smartphone to include iris recognition technology, after a very ... in May 2015, world,s first smartphone to have this ...
Breaking Biology News(10 mins):
(Date:12/1/2015)... ... 01, 2015 , ... Matthew “Tex” VerMilyea, PhD, HCLD, has joined Texas Fertility ... all IVF lab procedures as well as continue his research efforts into the emerging ... to Auckland, New Zealand to bring home a High Complexity Clinical Laboratory Director named ...
(Date:11/30/2015)... ... November 30, 2015 , ... ... join physicians, aesthetic practitioners and aesthetics professionals from Central America and abroad for ... held in Panama City, Panama Feb. 17-19, 2016. Testart will present and discuss ...
(Date:11/30/2015)... ... 30, 2015 , ... Global Stem Cells Group ... the Santiago Marriott. The Global Stem Cells Group GMP facility is equipped with ... qualified medical researchers and practitioners, experienced in administering stem cell protocols using highly ...
(Date:11/30/2015)... , Dec. 1, 2015  An interventional radiology technique shows ... the preliminary results of a study being presented today at ... North America (RSNA). --> ... for decades by interventional radiologists as a way to stop ... procedure as a means of treating obesity is new. ...
Breaking Biology Technology: