– Since the STAT3 gene is also abnormally expressed in many other cancers and autoimmune diseases, this finding has roused extensive interest, says Adjunct Professor Satu Mustjoki, the leader of this research.
LGL leukemia is a relatively rare, malignant blood disease of the mature T-cells and, in many cases, it is related to autoimmune diseases such as rheumatoid arthritis. The pathogenetic mechanism of the disease has been unknown and it has previously been unclear if the disease is an overreaction of the normal defense system or a malignant hematological disease.
One of the key symptoms of LGL disease is a low count of white blood cells, which may predispose the patients to life-threatening infections.
It was discovered that 40% of the patients suffering from LGL leukemia have a mutation in the STAT3 gene in a very restricted SH2 area, which has a key effect on the function of the gene. The STAT3 gene plays a key role in many cell signaling pathways.
– This is not an inherited gene mutation but a so-called acquired mutation, Dr. Mustjoki tells.
– The cause for the mutation is not known, but probably chronic viral infection or some other long-term antigen exposure can be predisposing factors.
In the future, this result can be utilized in diagnosing the disease and possibly also in treatment, since the first STAT3 inhibitors are already undergoing early clinical trials, Dr. Mustjoki says.
– In addition, the research discovered that those LGL patients who had a mutation in the STAT3 gene were also more likely to suffer from rheumatoid arthritis. Hence, the research group intends to clarify next if patients suffering from rheumatoid arthritis can be found with similar gene mutations.
If such mutations were to be found this would introduce new opportunities to the pathogenetic mechanisms of rheumatoid arthritis and other autoimmune diseases.
The research has been published in the New England Journal of Medicine.