Double Assault on Tough Types of Leukemias

Photo: Leukemia

New therapeutic strategy leads to
clinical trial and drug development
for leukemia with poor prognoses;
© panthermedia.net/Luk Cox

The disease is characterized by an overload of white blood cells that remain forever young because they cannot mature into specialized cells. 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 Doctor John Crispino. 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.

"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 do not 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 Doctor Jessica Altman.

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.

MEDICA.de; Source: Northwestern University Feinberg School of Medicine