A team of researchers belonging to the Massey Cancer Center of the Virginia Commonwealth University have discovered a mechanism which helps the leukemia cells to fight off anti-carcinogenic agents, known as histone deacetylase inhibitors or HDACI in short. The team led by Steven Grant went on to publish their findings in the Journal of Biological Chemistry. This discovery can now be utilized to treat patients with leukemia as well as other cancers of the blood more effectively.

Grant, the associate director concerned with translational research and a professor of medicine explained that the knowledge obtained from the study provides an important insight into the kind of resistance that the leukemic cells develop, which helps them to survive the cancer killing agents. Grant added that the knowledge would now help them to formulate a strategy by which the cancerous cells can no longer protect themselves against the treatment, thereby improving the rate of therapeutic success and, thereby, survival.

The primary basis of the discovery lies in the modification of NEMO, a protein. The researchers had prior knowledge of the activation of a protective mechanism by the leukemic cells on being exposed to HDACI. The survival pathway is known as NF-κB which inhibits the capability of the HDACI to trigger the self destructive mechanism ‘apoptosis’ in a cancerous cell.  The mechanism occurred due to modification of various receptors on the surface of the cell, thought the researchers previously. The latest study, however, discovered that HDACI in fact, damages the DNA of the cell nucleus which in turn triggers off the NF-κB pathway due to the modification of the protein, NEMO. The researchers further found out that the cancer killing abilities of the HDACI could be increased considerably by preventing the modifications of NEMO which then fails to activate the defensive mechanism via the NF-κB pathway.

The Massey Center at the VCU had been trying to find out the means to enhance the effectiveness of HDACI in leukemia and other related cancers of the blood. The HDACI has already been approved as an effective means for treating lymphomas. The team at VCU will now try to put their discovery to use by disrupting NEMO modifications via various pharmacologic agents as well as other drugs.

Source: Public Release By Virginia Commonwealth University on 30^th September 2010.

A recently published study in ‘Blood’, which serves as the official journal of the ‘American Society of Hematology’, substantiated that the presence of a particular protein can control certain characteristics of the blood stem cells thereby providing a better way of treating leukemic patients. The discovery was made by Dr. Tarik Möröy and his team. Dr. Cyrus Khandanpour, who is a post doctoral fellow, apart from being a medical doctor, working in Dr. Möröy’s laboratory, is the first author of the study, while Dr. Möröy himself serves as the President and Scientific Director of the ‘Hematopoiesis and Cancer Research Unit’ located at  the ‘Institut de Recherches Cliniques de Montréal’  better known as IRCM.

Dr. Möröy tells us that the transplantation of blood stem cells is vital for people suffering from leukemia as well as any other blood related disease. It forms one of the most important aspects of the therapy. The stem cells have the capability of reproducing the entire blood system including the red and white cells along with the platelets.

The therapeutic process involves subjecting the patient to chemotherapy, which destroys the blood system along with the disease. The patient is then given blood stem cells in order to recreate the blood system. The stem cells are either taken from the patients themselves before the chemotherapy or from a healthy donor.

The collection of the blood stem cells remains a difficult proposition as the cells tend to remain within the bone marrow in a dormant state. The cells have to be mobilized into the blood stream before they can be collected for transplantation. Harvesting the blood cells from a donor does not help all the time and about 10%-20% patients succumb to leukemia and its complications.

Dr. Möröy claims to have isolated a protein known as Gfi1b which has the capability of activating the blood cells within the bone, thereby facilitating its movement into the blood stream. The entire process thus becomes much easier and less time consuming.

The researchers hope that this discovery would make stem cell therapy more effective for patients suffering from leukemia. However, the actual procedure of regulating the stem cells from dormancy to its mobile form has not been deciphered as yet.

Dr. Moroy, along with his team, hopes to study the protein Gfi1b in more details which could eventually lead to a better understanding of its functions, thereby paving the way for a better regimen for patients who need to undergo the transplant.

Source: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/blood-2010-04-280305v1.