Chronic Myelogenous Leukemia (CML) Has An Answer Now!

Another plant extract called Forskolin has been found to be helpful in inhibiting the growth of chronic myelogenous leukemia (CML) cells in cultures and mice by up to 90 percent.

Forskolin is prepared from the root of the plant coleus forskohlii, a native of India that is used as an alternative remedy in other countries, and as an ornamental plant in the US.

CML, a malignant cancer of the bone marrow, results from mistakenly exchanging genetic material in chromosomes 9 and 22 during cell division. The translocation creates a new, fused gene (called BCR-ABL), that produces an enzyme called Bcr-Abl, which permanently "turns on" cell growth signals that are normally controlled by another group of enzymes phosphatases. Because of Bcr-Abl, production of white blood cells gets out of control, leading to CML.

At the early stage (chronic phase), the disease almost always responds to the anticancer drug Gleevec, which puts Bcr-Abl on hold. The drug was hailed as the first "wonder drug" for cancer when the Food and Drug Administration (FDA) approved it for CML treatment five year ago.

However, the disease has proven difficult for some patients. In a minority of patients who initially responded well to Gleevec, they acquired new mutations and developed resistance to the drug. In these patients, proliferation of white blood cells continues, leading the disease to the final (acute stage) called the blast crisis, where immature white blood cells infiltrate the blood and bone marrow.

Clinicians know the signs and symptoms of the different stages of CML, but until now, they are clueless about what causes the disease to progress.

In collaboration with an international group of researchers, Dr. Danilo Perrotti at the Ohio State University not only found the plant extract that effectively inhibits cell growth of CML, but also found that the progression of CML is due to the increased activity of Bcr-Abl enzyme.

Bcr-Abl stimulates a protein called SET, which, in turn, suppresses the phosphatase PP2A. PP2A acts otherwise as a tumour suppressor in the blast crisis, applying the brakes to growth signals stuck in the “on” position. When PP2A isn't working properly, cancer cells grow uncontrolled.

Earlier studies by Perrotti showed forskolin could restore PP2A function. In the current study, Perrotti and his research team tested the effects of forskolin on normal, Gleevec-sensitive and Gleevec-resistant CML cells, and discovered that the extract restored normal PP2A function, reduced the cancer cells' growth by up to 90 percent, and induced the death and differentiation of leukemia cells.

Forskolin had no adverse effects on the normal cells. It is currently used in Japan as a broncho- and vaso-dilator. It has been tested and found safe in clinical trials in Austria, among patients with asthma. The FDA has not approved it for use in the US.

In the study, Perrotti and his team treated leukemic mice with forskolin and then discontinued the treatment for a couple of weeks. After resuming the treatment, they observed that forskolin blocked Bcr-Abl activity and reinstated normal cell functioning in the mice that received forskolin, while others without treatment died.

The findings are significant because they may yield new treatment options – especially those with advanced CML, or who become resistant to the drug Gleevec.

"We believe these are significant findings," said Perrotti. "We have uncovered a key process that underlies progression in CML and identified an agent that can block it. We also have shown that forskolin can reinstate normal cell functioning, even in Gleevec-resistant cells that do not respond to any treatment currently available."

CML affects one or two people per 100,000 and accounts for 7 to 20 percent of cases of leukemia. Ionizing radiation is believed to trigger the chromosome abnormality that leads to CML. It takes years to develop CML.