Scientists have discovered an important clue that may explain why some people with leukemia also develop autoimmune diseases.
Researchers at the Garvan Institute of Medical Research found that certain inherited gene changes can create small numbers of abnormal immune cells that mistakenly attack the body’s own healthy tissues. The discovery helps connect two conditions that doctors have noticed are often linked but have not fully understood.
Leukemia is a type of blood cancer that begins in the bone marrow, where blood cells are made. It causes abnormal white blood cells to grow out of control. Autoimmune diseases are different. They happen when the immune system, which normally protects the body from viruses, bacteria, and cancer cells, starts attacking healthy organs and tissues instead.
Common autoimmune diseases include rheumatoid arthritis, which damages the joints, and aplastic anemia, a condition in which the bone marrow cannot produce enough healthy blood cells.
Doctors have long observed that some leukemia patients also develop autoimmune diseases. Until now, it has not been clear why these two illnesses are connected. The new study offers a possible answer by showing how certain genetic changes can affect a special group of immune cells called killer T cells.
Killer T cells are one of the body’s most important defenses. Their job is to find and destroy infected cells and cancer cells before they can spread. Normally, these cells are carefully controlled so they attack only dangerous targets. The immune system also has built-in safety checks that prevent these powerful cells from harming healthy parts of the body.
The research team found that changes in a protein called STAT3 can disrupt these safety controls. STAT3 plays a major role in helping immune cells grow, communicate, and respond to threats.
When this protein is changed by certain gene variations, killer T cells can become unusually active. Instead of stopping when their job is done, they continue growing and ignore the normal signals that keep the immune system balanced.
To understand how this happens, the scientists studied blood samples from children with rare inherited autoimmune diseases. They also used the gene-editing technology CRISPR-Cas9 to make precise changes to the STAT3 protein in mice. This allowed them to observe how the altered immune cells behaved.
The results were striking. The altered STAT3 protein caused killer T cells to grow larger, multiply more quickly, and bypass important immune checkpoints. These abnormal cells behaved like rogue immune cells that no longer followed the body’s normal rules.
Surprisingly, the researchers found that even a very small number of these rogue cells could have a major effect. If only about one to two percent of killer T cells became abnormal, they were still able to trigger autoimmune disease.
The findings may also improve future treatments. Doctors already use medicines called JAK inhibitors to treat some immune disorders and blood diseases.
By understanding which patients carry these specific gene changes, doctors may be able to choose treatments that are better matched to each person’s genetic makeup. This could make treatment more effective while reducing unwanted side effects.
The study also uncovered two stress-related cell receptor systems that appear to influence how these immune cells behave. Learning more about these pathways could give scientists additional targets for developing new medicines in the future.
Looking ahead, the researchers hope their work will lead to new screening tests. One day, doctors may be able to examine a simple blood sample, study the genes inside individual immune cells, and identify rogue killer T cells before they cause serious illness.
Detecting these harmful cells early could allow treatment to begin sooner and may help prevent autoimmune diseases from developing.
The study was led by Dr. Etienne Masle-Farquhar and published in the journal Immunity. The findings provide new insight into the close relationship between blood cancers and autoimmune diseases and show how modern genetic tools are helping scientists better understand the immune system.
This research may eventually lead to earlier diagnosis, more personalized treatments, and better outcomes for patients living with these challenging conditions.
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