- Researchers find that absence of
Uracil DNA Glycosylase (UNG) results in the shortening of B cell
- The presence of UNG protects B
- Inhibiting UNG could limit
proliferation of activated B lymphocytes in Non-Hodgkin's lymphoma.
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
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
and which highlights a new drug target that can be used to treat
‘Limiting B cell activation could limit non-Hodgkin's lymphoma.’
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.
Induced Deaminase (AID) and Development of non-Hodgkin's Lymphoma
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
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.
- 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.
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."
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
- 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)