Non-Hodgkin's Lymphoma Aided by Uracil DNA Glycosylase (UNG)

Uracil DNA glycosylase protects B cell DNA which allows the proliferation of activated B cells, highlighting a new target for non-Hodgkin’s lymphoma.

Researchers find that absence of Uracil DNA Glycosylase (UNG) results in the shortening of B cell telomeres.
The presence of UNG protects B cell telomeres.
Inhibiting UNG could limit proliferation of activated B lymphocytes in Non-Hodgkin’s lymphoma.

Researchers from The University of Miami Miller School of Medicine’s Sylvester Comprehensive Cancer Center and Institut de Recherches Cliniques de Montréal have found that Uracil DNA Glycosylase protects the ends of B cell chromosomes. This protection allows these antibody producing cells to proliferate during the invasion by foreign bodies.

Dr. Ramiro Verdun is the lead author of the study titled “UNG protects B cells from AID-induced telomere loss” which is published in The Journal of Experimental Medicine and which highlights a new drug target that can be used to treat Non-Hodgkin’s lymphoma.

Non-Hodgkins Lymphoma
Non Hodgkins Lymphoma is a cancer that affects the lymph tissues. It is made up of a wide array of subtypes.

‘Limiting B cell activation could limit non-Hodgkin's lymphoma.’

Non-Hodgkin’s Lymphoma

Non-Hodgkin’s lymphoma is a type of cancer that is found in the lymph nodes. It is most often found in a type of white blood cells called the B lymphocytes or B cells.

It generally affects people with weakened immune system like in people afflicted with HIV.
It is found more commonly in men than in women. Children my also be affected with non-Hodgkin’s lymphoma.
Non-Hodgkin’s lymphoma is detected by swelling in the lymph nodes in the neck, groin and underarms.
The individual could experience fever, pain, swelling, headache, loss of appetite and weight loss.

The current treatment modalities for non-Hodgkin’s lymphoma include radiation therapy and chemotherapy, new targets are necessary for a more specific treatment. The protection offered by uracil DNA glycosylase to the ends of B cells could be a possible target.

Activation Induced Deaminase (AID) and Development of non-Hodgkin's Lymphoma

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Hodgkin lymphoma is a type of cancer which originates from a specific type of white blood cells called lymphocytes and limits the body to fight infection.

When B cell encounters an invading cell, it releases an enzyme called activation induced deaminase (AID) that modifies the DNA. The enzyme creates changes to the DNA, mutations, that result in the production of B cells that have high affinity to the invading cells.

AID can lead to the mutation of other parts of the DNA of B-cell which are normally set right by repair mechanisms like UNG. If these mutations are not repaired, it can lead to the development of non-Hodgkin's lymphoma and other cancers.

Everolimus Combined with R Chop Safe for Treating Diffuse Large B Cell Lymphoma
The encouraging outcome, along with the worldwide availability of everolimus, make it potentially applicable to the large population of DLBCL patients.

The researchers in the study analyzed if the AID targeted the ends of mouse B cells. The ends of mouse B cells, or telomeres, were similar to immunoglobulins.

Results of the study

The study found that in the absence of UNG, the telomeres of B cells were affected by AID.
This led to the shortening of the B cell genes.
The shortened B cell telomeres limited the increase in the number of the activated B cells.
The presence of UNG

Repaired these gene mutations in the B cells
This restricted the shortening of telomeres
Allowed proliferation of activated B cells.

The effect of UNG is therefore to protect the telomeres of B cell and to promote its proliferation after activation. This will aid in mounting an effective immune response against the invading organism.

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Overweight and obesity during adolescence was associated with a 25 percent increased risk of a type of cancer of the lymphatic system, in later life

In non-Hodgkin's lymphoma, however, there is an increased secretion of AID to allow continuous proliferation. The study researchers found that when UNG was blocked, it lead to the blockage in the growth and proliferation of AID-expressing B cells.

Dr. Verdun says “So UNG can contribute to lymphomagenesis by protecting telomeres from AID-induced damage. We show that cancerous human B cells expressing AID require UNG for proliferation, suggesting that targeting UNG may be a means to delay the growth of AID-positive cancers.”

The prognosis of a patient suffering from non-Hodgkin's lymphoma depends upon the response to chemotherapy, stage of the disease and the progress of the disease condition. A targeted therapy that tries to starve the source of cancer will aid in providing better treatment and care for patients with Non-Hodgkin's lymphoma.

References:

What is Non-Hodgkin's Lymphoma? - (http://www.cancer.org/cancer/non-hodgkinlymphoma/detailedguide/non-hodgkin-lymphoma-what-is-non-hodgkin-lymphoma)
All About Non-Hodgkin Lymphoma - (https://medlineplus.gov/ency/article/000581.htm)

Source-Medindia