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!
Advanced analysis of brain structure shape may track progression to Alzheimer's disease
26.10.2016 | Massachusetts General Hospital
Indian roadside refuse fires produce toxic rainbow
26.10.2016 | Duke University
Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.
So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
28.10.2016 | Power and Electrical Engineering
28.10.2016 | Physics and Astronomy
28.10.2016 | Life Sciences