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 important 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.”

Funding from the National Cancer Institute, the Paul and Mary Haas Chair in Genetics, a Lauri Strauss Discovery grant award, the Kimmel Foundation and the CLL Global Research Foundation supported this research.

Source-Bio-Bio Technoloy

Related medicine news :

1. Cyclosporin A Treats Leukemia Complications
2. Leukemia pill shows promise against stomach cancer
3. Aspirin Lowers Leukemia Risk
4. Hope for Chemo-Resistant Leukemia Patients
5. Genes Found To Help Leukemia Treatment
6. Looking Towards More Effective Leukemia Treatment
7. Diet Found To Offer Protection Against Leukemia
8. Exposure To Night Light may Increase The Risk Of Leukemia
9. Skin Allergies Found To Increase The Risk Of Leukemia
10. Understanding Gene Profiles Could Help Cure A Resistant Form Of Leukemia In Kids
11. Night Light Found To Increase The Risk Of Leukemia
Post Your Comments:

(Date:11/30/2015)... ... November 30, 2015 , ... The recently published 32nd ... System (NPDS) reveals that in 2014, someone called a poison center about every ... of which were human exposure cases. , The American Association of Poison Control ...
(Date:11/30/2015)... , ... November 30, 2015 , ... ... promoting breast and prostate cancer education and prevention—is joining forces with the award-winning ... philanthropy and Hollywood elegance on December 7, 2015 at the Union League of ...
(Date:11/30/2015)... (PRWEB) , ... November 30, 2015 , ... ... Reports magazine, quoted Michael Hansen, Ph.D., a senior scientist at Consumer Reports as ... more so for a child’s exposure limits. , The original Nov 2015 CR ...
(Date:11/30/2015)... ... November 30, 2015 , ... An inventor from Charlottesville, Va., ... womb. "My last baby had high blood pressure due to loud noises," she said, ... their babies from noise pollution as well as radio waves and microwaves." , The ...
(Date:11/30/2015)... ... November 30, 2015 , ... ... automated breast density assessment and enterprise analytics solutions, here at the 101st ... (South Hall booth #2377). Volpara’s quantitative breast imaging tools enable personalized measurements ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... Nov. 30, 2015  PTS Diagnostics, the U.S.-based manufacturer ... analyzers, A1CNow ® systems, and PTS Detect™ ... of patents that will propel the company into the ... Europe . The technology is a ... those on smartphones and tablets, and uses test strip ...
(Date:11/30/2015)... , Nov. 30, 2015 Oramed Pharmaceuticals ... focused on the development of oral drug delivery systems, ... agreements valued at up to $50,000,000 with Hefei Tianhui Incubator of Technologies ... oral insulin capsule, ORMD-0801, in China ... Macau . The agreements were signed at ...
(Date:11/30/2015)... , Nov. 30, 2015 Cumberland Pharmaceuticals (CPIX), today ... live at on December 3, 2015. TIME: ... TIME: 3:15p.m. ET LINK: --> ... --> ... where investors are invited to ask the company questions in ...
Breaking Medicine Technology: