Navigation Links
Leukemia drug turns mini-molecules up, cancer genes down

New research shows that a form of vitamin A used to treat acute promyelocytic leukemia induces changes in an unusual class of small molecules called microRNAs (miRNAs) in the leukemic cells.

The study also shows that three of these miRNAs inhibit the action of two genes important for cancer development, helping to explain how the drug works.

The drug is called all-trans-retinoic acid (ATRA) and it is considered the gold standard for treating the disease.

The study showed that ATRA raises the levels of three particular miRNAs in leukemia cells and that this rise coincides with a fall in activity of two important cancer-causing genes. The three are identified as miRNA-15b, miRNA-16-1 and let-7.

Two of these, miRNA-15b and miRNA-16-1, reduce the activity of the Bcl-2 gene, which is over-active in many kinds of cancer. The protein produced by this gene blocks the normal process of cell death and helps keep cancer cells alive long after they should have died.

The remaining miRNA molecule, let-7, lowered the activity of the Ras oncogene, an important cancer-causing gene. (Oncogenes are normal genes that when mutated lead to cancer.)

Researchers at the Ohio State University Comprehensive Cancer Center led the study, which was published in a recent issue of the journal Oncogene.

"The findings are important because they tell us that some miRNAs switch off genes that promote cancer," says first author Ramiro Garzon, a hematologist and oncologist at Ohio State's James Cancer Hospital and Solove Research Institute.

Acute promyelocytic leukemia occurs when cells that give rise to a form of white blood cell become stuck at an immature stage. The immature cells accumulate until they crowd out healthy white cells in the blood and bone marrow.

"Our findings suggest that these three miRNAs help re-program the malignant cells to a more normal state," Garzon says, "and that they are also impo rtant for normal differentiation."

In this study, the researchers used leukemia cells grown in the laboratory and cells donated by patients to study how the drug ATRA affects miRNA levels and how those changes affect the cells.

The investigators exposed the leukemia cells to the drug for up to 96 hours, causing the cells to mature. The treatment increased the level of eight miRNAs and a drop in one compared with untreated cells.

Of these, the researchers focused on miRNA-15b and miRNA-16-1, which are known to regulate the activity of the Bcl-2 gene. They found that high levels of the two miRNAs were associated with low Bcl-2 activity.

Next, they showed that the two miRNAs actually caused the drop in Bcl-2 activity. They did this by adding additional amounts of the two miRNAs to leukemia cells not treated with ATRA. Restoring the miRNAs caused a strong drop in Bcl-2 levels.

The researchers then looked at miRNA let-7, a known regulator of the Ras oncogene, and likewise found that high levels of this miRNA were associated with low Ras activity.

They established a cause and effect relationship as before, by adding additional let-7 to untreated leukemia cells.

"Overall," Garzon says, "our findings show that ATRA induces the expression of these three miRNAs, and through them regulates genes that need to be silenced for the cell to differentiate."


Source:Ohio State University

Related biology news :

1. Leukemia Drug Breakthrough Study In New England Journal Of Medicine
2. Protein That Promotes Survival Of Stem Cells Might Be Key To Poor Leukemia Prognosis
3. Genetically Modified Natural Killer Immune Cells Attack, Kill Leukemia Cells
4. Loosen up, DNA: Leukemia gene changes genetic packaging
5. Lack of enzyme turns fat cells into fat burners
6. Programmable cells: Engineer turns bacteria into living computers
7. Gene therapy turns off mutation linked to Parkinsons disease
8. Hopkins researchers discover genetic switch that turns off an oxygen-poor cells combustion engine
9. Jefferson researchers uncover new way nature turns genes on and off
10. Viral DNA sequence a possible trigger for breast cancer
11. Enzyme, lost in most mammals, is shown to protect against UV-induced skin cancer
Post Your Comments:

(Date:11/18/2015)... , Nov. 18, 2015  As new scientific discoveries ... doctors and other healthcare providers face challenges in better ... and patients. In addition, as more children continue to ... patient,s adulthood and old age. John M. ... Children,s Hospital of Philadelphia (CHOP) . --> ...
(Date:11/17/2015)... 17, 2015  Vigilant Solutions announces today that Mr. ... of Directors. --> --> ... from the partnership at TPG Capital, one of the ... $140 Billion in revenue.  He founded and led TPG,s ... TPG companies, from 1997 to 2013.  In his first ...
(Date:11/12/2015)... Mass. , Nov. 12, 2015  Arxspan ... Institute of MIT and Harvard for use of ... discovery information management tools. The partnership will support ... both biological and chemical research information internally and ... will be used for managing the Institute,s electronic ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... November 24, 2015 , ... The United States Golf ... the 2016 USGA Green Section Award. Presented annually since 1961, the USGA Green Section ... her work with turfgrass. , Clarke, of Iselin, N.J., is an extension ...
(Date:11/24/2015)... 24, 2015 /CNW/ - iCo Therapeutics ("iCo" or "the ... results for the quarter ended September 30, 2015. ... dollars and presented under International Financial Reporting Standards ... ," said Andrew Rae , President & ... are not only value enriching for this clinical ...
(Date:11/24/2015)... 2015 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ:  AEZS) (TSX: AEZ) ... of the Toronto Stock Exchange, confirms that as of ... corporate developments that would cause the recent movements in ... --> About Aeterna Zentaris Inc. ... Aeterna Zentaris is a specialty biopharmaceutical company engaged ...
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... This fall, ... at competitive events in five states to develop and pitch their BIG ideas to ... from each state are competing for votes to win the title of SAP's Teen ...
Breaking Biology Technology: