Blood Cancer Treatment Outcome Depends on Genetic Make Up of Proteins

The activity of the immune system and the ability to fight cancer is decided by the body's genetic make up. The genetic make up decides the type of protein that the individual inherits. This can influence the risk of certain types of auto-immune diseases and also the individual's response to cancer treatment.

The study was conducted by a team of researchers at the University of Birmingham in conjunction with researchers from Birmingham's Queen Elizabeth Hospital.

The study focuses on a protein called ULBP6. This protein helps in the removal of damaged cells.

Proteins are made up of organic compounds called amino acids.

Proteins do most of the work in cells and are required for the structure, function, and regulation of the body's tissues and organs.

It plays an important role in:

• breaking down food
• growth and repair of body tissue
• Performance of many other body functions

Lead author of the study Professor Paul Moss from the University of Birmingham's Institute of Immunology and Immunotherapy, said "We worked on a protein called ULBP6 which leads to the removal of damaged cells and an interesting observation has been that there are two types of this protein found in different people. This is important as previous studies have shown that the type of protein that we inherit from our parents can influence our risk of auto-immune disease and affect how we respond to some forms of cancer treatment."

ULBP6 Protein

The ULBP6 protein is found on the surface of damaged cells, including several types of cancer cells.

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This protein acts as a 'flag' that signals the white cells in the immune system to kill the damaged cell.

In the study, the research team found that there are two major types of the protein that is inherited. People inheriting a certain subtype have shown poor outcome after stem cell transplantation therapy.

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This procedure also referred to as bone marrow transplant is used to treat leukemia.

Proteins are made up of many smaller units called amino acids that are attached to one another in long chains. There are a total of 180 amino acids in the body.

The discovery shows that the two subtypes of the ULBP6 differ only by two amino acids.

Professor Ben Willcox, also from the University of Birmingham's Institute of Immunology and Immunotherapy, said "It has surprised us that this can have such an important influence on patient outcomes."

Strong Bond with Receptor

The study showed that one form of ULBP6 forms a very strong bond with its receptor NKG2D on the immune system. This form also termed as the 'sticky' form binds 10 times more strongly with its receptor.

But the strong bond reduces the killing of the damaged cells by the immune system, rather than increasing it.

"In addition, when the protein is released into the local environment it can act to block the signaling pathway." Willcox added.

This information could be used to improve the outcome for patients undergoing stem cell transplantation.

Conclusion

Alasdair Rankin, Director of Research at Bloodwise, said "For some people with leukemia and other types of blood cancer, stem cell transplantation can mean the difference between life and death. But a stem cell transplant is a grueling procedure which sadly does not always work, so we need research to improve success rates."

Though the findings will not help to change the type of care, it may help us understand why transplants work less well in some people. This knowledge is important for developing better transplant therapy for more people suffering from blood cancer.

The study is published in Science Signaling.

References:

1. Amino acids - (https://medlineplus.gov/ency/article/002222.htm)
2. Paul Moss et al. A disease-linked ULBP6 polymorphism inhibits NKG2D-mediated target cell killing by enhancing the stability of NKG2D-ligand binding. Science Signaling; (2017) DOI: 10.1126/scisignal.aai8904

Source-Medindia