Navigation Links
A gene within a gene contributes to the aggressiveness of acute myeloid leukemia
Date:4/21/2014

COLUMBUS, Ohio A small gene that is embedded in a larger, well-known gene is the true leukemia-promoting force usually attributed to the larger gene, according to a new study by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James).

The findings are published in the journal Science Signaling.

The larger host gene is called BAALC (pronounced "Ball C"). The smaller embedded gene is called microRNA-3151 (miR-3151). The study investigated the degree to which each of the genes contributes to the development of acute myeloid leukemia (AML).

"We discovered that the smaller microRNA gene, and not the larger host gene, is the major oncogenic driver of the two molecules in AML," says principal investigator Albert de la Chapelle, MD, PhD, professor of Medicine and the Leonard J. Immke Jr. and Charlotte L. Immke Chair in Cancer Research.

"When both genes are highly expressed, it means a bad prognosis for patients, but our experiments indicate that it is high expression of miR-3151 that really matters. Overexpression of BAALC alone had only limited cancer-causing activity," he says.

The researchers discovered that miR-3151 promotes the development of leukemia by blocking a gene called TP53. Normally, TP53 is a central "tumor-suppressor" gene that protects against cancer by causing a cell with serious gene damage to self-destruct. "When miR-3151 blocks TP53 in the tumor cells, it enables the cells to survive, divide and grow faster," says co-senior author Clara D. Bloomfield, MD, Distinguished University Professor and Ohio State University Cancer Scholar.

"We also show that miR-3151 promotes growth in malignant melanoma cells in the same way, suggesting that the molecule might play a role in solid-tumor development," says Bloomfield, who is also senior adviser to the OSUCCC James and holds the William Greenville Pace III Endowed Chair in Cancer Research.

Last, the researchers show that miR-3151 overexpression may be inhibited by the drug bortezomib, a proteasome inhibitor, suggesting a possible therapy for miR-3151 overexpression.

MicroRNAs are a class of molecules that cells use to help regulate the kinds and amount of proteins they make. "About one-third of the several hundred known human microRNAs are encoded in host genes," says first author Ann-Kathrin Eisfeld, MD, a postdoctoral researcher who works in the laboratory of study co-authors de la Chapelle and Bloomfield.

Specifically, they are located in areas of genes called introns, short stretches of DNA that are not involved in making a protein. "We know very little about how microRNAs located within introns are regulated and how they interact with their host genes," Eisfeld says. "These findings provide an important example of that interaction."

The researchers found, for example, that miR-3151 has the capability to be active on its own, independent of the host gene.

For this study, de la Chapelle, Bloomfield, Eisfeld and their colleagues used human AML cells, cell lines and an animal model to investigate the overexpression of miR-3151 and BAALC in older patients with cytogenetically normal AML. Key technical findings include:

  • MiR-3151 directly targets PT53 and seven other genes in the TP53 pathway;
  • Overexpressing miR-3151 promotes AML-cell growth;
  • BAALC overexpression enhances that effect while blocking miR-3151 or overexpressing TP53 reverses it;
  • miR-3151 alone and in combination with BAALC promotes leukemia development in an animal model.


'/>"/>

Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Wexner Medical Center
Source:Eurekalert

Related medicine news :

1. For Healthier Eating, Keep Fruits, Veggies Within Reach
2. Ketamine improved bipolar depression within minutes
3. Family first - caring within UK Bangladeshi and Pakistani communities
4. Researchers find new target deep within cancer cells
5. Immune responses can be generated locally within human melanoma skin metastases
6. Strategy May Help ER Docs Spot Heart Attacks Within an Hour
7. Smoking After Stroke Triples Risk of Death Within Year: Study
8. ACNP: Novel NMDA receptor modulator significantly reduces depression scores within hours
9. RazorInsights Reports Inclusion in KLAS Data, Gaining Traction within Community Hospital Segment
10. Ovarian cancer stem cell study puts targeted therapies within reach
11. Hearing Aid Device Expert of Upstate Hearing Instruments Provides 7 Key Tips to Encourage Hearing Aid Adoption within the Elderly Populations
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Many families ... However, many long-term care insurance companies have a waiver for care if the client ... elimination period, when the family pays for care, is often waived, so the benefits ...
(Date:10/13/2017)... New York, NY (PRWEB) , ... October 13, 2017 , ... ... most influential people in business to advocate for action towards gender equality at their ... 18,000 views from around the globe, and reached a social audience of over 3 ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer at ... of the most popular and least understood books in the Holy Scriptures, Revelation. The ... that have baffled scholars for centuries. Many have tossed it off as mere rubbish, ...
(Date:10/13/2017)... ... October 13, 2017 , ... ... Agile Software Development, has been awarded a contract by the Center for Medicare ... (BPA) aims to accelerate the enterprise use of Agile methodologies in a consistent ...
(Date:10/13/2017)... ... 2017 , ... “America On The Brink”: the Christian history of the United ... the creation of published author, William Nowers. Captain Nowers and his wife, Millie, ... spent thirty years in the Navy. Following his career as a naval aviator ...
Breaking Medicine News(10 mins):
(Date:9/22/2017)... Md. , Sept. 22, 2017  As the ... Republican Senators Bill Cassidy (R-LA) and ... Information notes that the medical device industry is in ... medical device tax, the 2.3% excise tax on medical ... But they also want covered patients, increased visits and ...
(Date:9/19/2017)... LOUISVILLE, Ky. , Sept. 19, 2017   ZirMed ... and predictive analytics, today announced that it has been ranked ... the Black Book™ Rankings 2017 User Survey. ZirMed ... software solution for large hospitals and medical centers over 200 ... in Black Book,s healthcare technology user survey history. ...
(Date:9/13/2017)... 13, 2017   OrthoAtlanta has been named the ... Host Committee (AFHC) for the 2018 College Football Playoff (CFP) ... at Mercedes-Benz Stadium in Atlanta, Georgia . ... "I,m In" campaign, participating in many activities leading up to, ... ...
Breaking Medicine Technology: