Featured Research

from universities, journals, and other organizations

Double assault on tough types of leukemias

Date:
September 20, 2012
Source:
Northwestern University
Summary:
Investigators have identified two promising therapies to treat patients with acute megakaryocytic leukemia, a rare form of leukemia where the number of cases is expected to increase with the aging population. One of the drugs, Alisertib, was potent against the proliferation of cancer cells and reversed the disease in mice. Clinical trials are slated for 2013.

Investigators at Northwestern University Feinberg School of Medicine have identified two promising therapies to treat patients with acute megakaryocytic leukemia (AMKL), a rare form of leukemia where the number of cases is expected to increase with the aging population.

The disease is characterized by an overload of white blood cells that remain forever young because they can't mature into specialized cells. Published in a recent issue of the journal Cell, the study found that the drug with the generic name alisertib (MLN8237), induced division and growth of healthy cells to overtake the proliferation or "blasts" of immature cells.

In the study, a mouse model with this leukemia that was treated with alisertib showed a striking reduction in the number of leukemia cells, including dramatic reductions in overwhelming white cell counts and the weights of their spleens and livers, which are indications of leukemia.

Alisertib has been tested before in humans with limited success to treat other types of leukemia and lymphoma, a cancer of the immune system. However, the drug should be effective against AKML in humans because it specifically targets the enzyme Aurora A kinase, said study senior author John Crispino, the Robert I. Lurie, MD, and Lora S. Lurie Professor of Hematology/Oncology at Feinberg. In normal cell development, this enzyme enables healthy cells to proliferate correctly, but with leukemia, is also allows adolescent cells to multiply unchecked if they are in the mix.

Crispino also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

"Alisertib was really potent against the proliferation of cancer cells," Crispino said. "We were incredibly excited when we found that the drug we predict will reverse AMKL is already far along in clinical development. The fact that we don't have to start from scratch means we could be years closer to finding an effective therapy."

Crispino expects alisertib will be a more gentle cancer drug without the ravaging side effects of conventional chemotherapies. This is because the drug specifically targets a key enzyme, avoids healthy cells in the bone marrow and blood, and will probably be more effective at lower doses than drugs tested in previous studies.

"This study has given us a scientific rationale to take this drug to an early phase clinical trial in this very challenging form of leukemia," said Jessica Altman, M.D., assistant professor in hematology/oncology at Feinberg and an oncologist at Northwestern Memorial Hospital. Altman also is a member of the Lurie Cancer Center. Together with other leukemia specialists, she is designing a multi-center clinical trial planned to open in 2013.

Investigators also identified another attack plan for other types of leukemias. Sifting through 9,000 chemical compounds during the study, they found that dimethylfasudil boosted the number of mature bone marrow cells and shot down malignant ones.

Dimethylfasudil could be useful against AMKL and tolerated better by patients, Crispino says. However, he adds that alisertib is moving forward now because there is urgent need and the drug is available. Meanwhile, Crispino's team and other scientists at Northwestern's Center for Molecular Innovation and Drug Discovery are developing the compound dimethylfasudil into an acceptable anticancer drug for clinical trials, which may take two to three years.

Investigators believe dimethylfasudil may be valuable to fight other types of leukemias because it has broad action against other enzymes that let cancer cells reproduce.


Story Source:

The above story is based on materials provided by Northwestern University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Qiang Wen, Benjamin Goldenson, Serena J. Silver, Monica Schenone, Vlado Dancik, Zan Huang, Ling-Zhi Wang, Timothy A. Lewis, W. Frank An, Xiaoyu Li, Mark-Anthony Bray, Clarisse Thiollier, Lauren Diebold, Laure Gilles, Martha S. Vokes, Christopher B. Moore, Meghan Bliss-Moreau, Lynn VerPlank, Nicola J. Tolliday, Rama Mishra, Sasidhar Vemula, Jianjian Shi, Lei Wei, Reuben Kapur, Cécile K. Lopez, Bastien Gerby, Paola Ballerini, Francoise Pflumio, D. Gary Gilliland, Liat Goldberg, Yehudit Birger, Shai Izraeli, Alan S. Gamis, Franklin O. Smith, William G. Woods, Jeffrey Taub, Christina A. Scherer, James E. Bradner, Boon-Cher Goh, Thomas Mercher, Anne E. Carpenter, Robert J. Gould, Paul A. Clemons, Steven A. Carr, David E. Root, Stuart L. Schreiber, Andrew M. Stern, John D. Crispino. Identification of Regulators of Polyploidization Presents Therapeutic Targets for Treatment of AMKL. Cell, 2012; 150 (3): 575 DOI: 10.1016/j.cell.2012.06.032

Cite This Page:

Northwestern University. "Double assault on tough types of leukemias." ScienceDaily. ScienceDaily, 20 September 2012. <www.sciencedaily.com/releases/2012/09/120920153317.htm>.
Northwestern University. (2012, September 20). Double assault on tough types of leukemias. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2012/09/120920153317.htm
Northwestern University. "Double assault on tough types of leukemias." ScienceDaily. www.sciencedaily.com/releases/2012/09/120920153317.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) — New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) — Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) — Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) — Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins