Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Double assault on tough types of leukemias

21.09.2012
New therapeutic strategy leads to clinical trial, drug development for leukemia with poor prognoses

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.

The study was funded by the Samuel Waxman Cancer Research Foundation, Leukemia & Lymphoma Society, and National Cancer Institute of the National Institutes of Health grant R01CA101774.

Other authors of the paper from Northwestern are first author Qiang Wen, M.D., research assistant professor of hematology/oncology, Zan Huang, former postdoctoral student and now professor at Wuhan University in China, Lauren Diebold, doctoral student, Laure Gilles, postdoctoral fellow, and Benjamin Goldenson, graduate student in the Medical Scientist Training Program. Investigators from 14 other national and international institutions are also study authors.

Marla Paul | EurekAlert!
Further information:
http://www.northwestern.edu

Further reports about: AMKL Double blood cell bone marrow cancer cells cancer drug healthy cell white blood cell

More articles from Health and Medicine:

nachricht Vanishing capillaries
23.03.2017 | Technische Universität München

nachricht How prenatal maternal infections may affect genetic factors in Autism spectrum disorder
22.03.2017 | University of California - San Diego

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>