Navigation Links
Mouse Gene With Gene Stutter Will Help Leukemia Research

Cancer researchers have developed a new strain of mice that should help reveal how an unusual change in a certain gene contributes to a particularly deadly form of acute myeloid leukemia (AML).//

A study of the strain by its developers at the Ohio State University Comprehensive Cancer Center (OSUCCC) suggests that the genetic change comes early in the disease, and that it over-activates a second gene that helps govern blood cell development.

The genetic change, known as a partial tandem duplication, is located in a gene called MLL (for mixed-lineage leukemia). A partial tandem duplication is a type of gene mutation that occurs when a section of a gene is repeated, like a stutter in the gene’s DNA.

The new mouse model should help leukemia researchers to learn how this mutation contributes to AML development, and it may lead to new ways to treat, diagnose and perhaps prevent the disease.

The findings were published online Sept. 14 in the Journal of Clinical Investigation.

“When leukemia strikes, it’s like a hurricane arriving without an advance weather forecast – you have no information about how it got there, and it’s a level-5 storm,” says Michael A. Caligiuri, principal investigator of the study and director of the OSUCCC.

“Studying live models like this mouse strain helps us begin to understand the earliest events in the development of leukemia. This in turn will someday allow us to understand what causes leukemia in people, predict who is at greatest risk and prevent leukemia from ever developing in those patients.”

Genes store information for a protein. Mutations can alter the protein, perhaps making it function differently. In this case, the duplication within the MLL gene contributes to an aggressive form of AML. This new study begins to reveal how it does so.

AML will strike an estimated 10,000 Americans this year, and about 45 percent of those will have cancer cells with normal-looking chromosomes. Some 4-7 percent of patients in this group will have cancer cells with this mutation. Their disease is likely to respond poorly to therapy and their remissions will be short.

Several years ago, Caligiuri, together with OSUCCC researchers Clara D. Bloomfield and Carlo M. Croce, discovered this mutation in the MLL gene. The MLL gene stores information for a protein that helps regulate the activity of other genes called Hox (for homeobox) genes, which control many aspects of development.

To make the mouse strain, Caligiuri and his colleagues used genetic engineering techniques to remove a section of the normal MLL gene from one animal and insert it into the MLL gene of another. The result is a strain of mice with a mutation that mimics the one that occurs in human leukemia.

The researchers then looked to see how the mutation affected the animals. The most obvious changes was a missing or rudimentary 13th rib and an additional vertebra in the lower backbone. This suggested the mutation was affecting Hox genes, some of which govern the growth and development of the skeleton and of blood cells.

Next, the researchers examined cells in the bone marrow and spleen that give rise to blood cells. The cells looked normal, as did their numbers. But when the cells were grown in a laboratory test tube, those with the mutation grew far faster and formed much larger colonies than control cells without the mutation.

In addition, cells with the mutation could be used to start new colonies four or more times, while control cells could not. This showed that cells with the mutation lived longer than normal.

Rapid proliferation and unusually long life are features of cancer cells.

Three Hox genes could be involved in the increased proliferation of the progenitor cells. An analysis showed that of the three, the HoxA9 gene was overactive. Its protein was being made at levels much higher than normal.

Furthermore, the researchers also discovered changes that might explain why the gene is overactive. For example, they found that proteins called histones, which help control a gene’s activity, were being altered.

“We show that the histones are being modified in ways that can increase the activity of the HoxA9 gene,” says first author Adrienne M. Dorrance, a graduate student in Caligiuri’s laboratory and the recipient of the Lady Tata Memorial Trust Award for her work on this gene. “We believe that the mutation is somehow activating this modification.”

In spite of these changes, the mouse strain does not develop leukemia.

“The failure of the mice to develop leukemia suggests that the partial tandem duplication occurs early in the leukemic process and that additional mutations are needed for the disease to occur,” Dorrance says. “That’s what we’re now focused on.”

“Ultimately,” Caligiuri says, “we believe that this mouse will further our understanding of how leukemia develops and open up new therapeutic options for this group of AML patients with a poor prognosis.”


SRM
'"/>




Related medicine news :

1. Mouse Allergen Found In Homes Could Trigger Asthma In Kids
2. Researchers Develop Mouse Model Of Brain Tumor
3. German Scientists Create Stem Cells From Mouse Testes
4. Mouse Models To Determine The Cause Of Aggressive Leukemia
5. Mouse Model Beneficial to Study of Head and Neck Cancer
6. Scientists Discover New RNAs in Mouse Testicles
7. Scientists Isolate Leukemia Stem Cells in Mouse Model
8. Mouse Model Demonstrates Immune System Reaction In Chlamydia Infection
9. Rett Syndrome Reversed in Genetic Mouse Model
10. Treatment Extends Survival in Mouse Model of Spinal Muscular Atrophy
11. Mouse Study Suggests Anxiety Disorders Take Root in Infancy
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:5/24/2016)... (PRWEB) , ... May 24, 2016 , ... ... to family wealth and to housing, with more advantaged communities providing richer opportunities. ... five types of interventions: (a) school improvement policies; (b) school choice policies; (c) ...
(Date:5/24/2016)... ... May 24, 2016 , ... Regenerative Medicine is being transformed by ongoing ... therapy technology, protocols and patient results as have been achieved with Okyanos Cell ... accessible standard of care for patients worldwide. , As the Medical Advisory Chairman at ...
(Date:5/24/2016)... ... , ... Backed by decades of experience, Metroloji Okulu works ... best suited solution to meet regulatory requirements. Their professional staff also performs on-site ... , Metroloji Okulu specializes in MadgeTech’s line of medical and pharmaceutical data ...
(Date:5/24/2016)... ... May 24, 2016 , ... ... Jonathan (Jon) Otterstatter to its board of directors. Otterstatter is co-founder, ... in the development of technological innovations that lead to broad-based healthcare solutions. , ...
(Date:5/24/2016)... ... , ... WaterAid launched the #perioddrama campaign to mark Menstrual Hygiene Day on May ... the world who do not have access to a toilet, even when they’re on their ... of #perioddrama. The (sometimes hilarious) results help shine a light on the awkwardness that women ...
Breaking Medicine News(10 mins):
(Date:5/24/2016)... LAWRENCE, Mass. , May 24, 2016  NxStage ... medical technology company focused on advancing renal care, today ... Officer, plans to participate in the following schedule of ... will be made available at http://ir.nxstage.com/ . ... Jefferies Healthcare Conference NY, NY           Friday, ...
(Date:5/24/2016)... HONG KONG , May 24, 2016 /PRNewswire/ ... primer stent de doble terapia del mundo, introduce ... fístula arteriovenosa. OrbusNeich, una compañía global ... cambian las vidas, ha expandido su cartera incluyendo ... catéteres balón JADE™ y Scoreflex™ PTA son los ...
(Date:5/24/2016)... Een app die artsen over ... patiënten kunnen behandelen, hun kennis kunnen delen en van ... nieuwe en revolutionaire MDLinking App, ontwikkeld door een internationale ... Hans Flu en oncologisch chirurg dr. Gijs van ... wordt op dinsdag 24 mei officieel gepresenteerd op het ...
Breaking Medicine Technology: