Protein silencing could reverse leukemia

October 23rd, 2008 - 1:35 pm ICT by IANS  

Washington, Oct 23 (IANS) Blocking signals from a protein that activates immune system cells could help reverse a rare form of blood cancer, according to researchers.Physicists and oncologists, who combined computer modelling and molecular biology, said the breakthrough could provide more efficient ways of targeting diseases such as leukemia, and help in the potential development of vaccines for viruses that cause AIDS.

The immune system has a two-part strategy when dealing with infections. It generates antibodies that bind with bacteria and viruses to neutralise them. For a short time, the immune system also produces large numbers of a type of white blood cell, cytotoxic T-cell that kills other infected cells.

Once the pathogens are eliminated, these killer T-cells quickly die on their own, save for a few that remain in case the same infection returns. But in rare cases, these cells fail to follow their scripted lifecycle, according to a Penn State University release.

“When these cells don’t normally die, they expand gradually over time and start attacking the body itself,” said Thomas Loughran, co-author and director of Penn State University Hershey Cancer Institute.

“They can attack the joints to cause autoimmune diseases such as rheumatoid arthritis, and attack the bone marrow to cause leukemia.”

Loughran, professor of medicine, and his Penn State colleagues are trying to tease out the conditions that cause the abnormal expansion of T-cells and trigger a disease known as large granular lymphocyte leukemia.

So they constructed an intricate computer model illustrating the signalling network involved in the activation of the T-cells, as well as their programmed death.

The network model strings together complex data of molecular pathways inside a cell involving hundreds of genes and proteins and tries to predict an outcome based on how the genes and proteins interact.

“The interactions among proteins make them turn on or off to get billions of possibilities with hundreds of proteins,” said Reka Albert, co-author and Penn State associate professor of physics and biology.

Albert explains that the model could help researchers zero in on the exact location of the signalling abnormalities that are keeping T-cells from dying. Once that is known, specific genes or proteins could be targeted with drugs to get rid of the abnormality.

Sifting through the billions of possibilities projected by the model, the researchers have found two proteins - IL-15 and PDGF - that appear to be crucial in keeping the T-cells alive. While IL-15 is key to the survival and activation of T-cells, PDGF stimulates the growth of those cells.

“You need the presence of both these proteins to create conditions in which the cytotoxic T-cells can proliferate,” said Loughran, whose team’s findings were published this week in the Proceedings of the National Academy of Sciences.

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