A gene is a set of instructions for building a protein, and a gene mutation is a change in those instructions that can alter a protein’s function. The TET2 gene provides the code for making the TET2 protein. A TET2 mutation is an acquired change, meaning it is not inherited but arises in a single cell during a person’s life. Any cells that descend from that original altered cell will also carry the same mutation.
The Role of the TET2 Gene
The TET2 gene provides instructions for a protein that acts as a tumor suppressor, which helps prevent cells from growing and dividing uncontrollably. While the TET2 protein is found throughout the body, it has a significant function in the hematopoietic stem cells within the bone marrow. These are the specialized cells that develop into all types of blood cells, including red blood cells, white blood cells, and platelets.
The TET2 protein is involved in a process called DNA demethylation. Methyl groups are chemical tags that act as “off” switches on genes, and the TET2 protein works by removing them. This process is part of epigenetics, which modifies how genes are expressed without changing the DNA sequence.
By removing methyl groups, the TET2 protein allows other genes to be expressed properly. This ensures that blood stem cells develop and mature correctly and that their growth remains under control.
Associated Health Conditions
A TET2 mutation can lead to a condition called Clonal Hematopoiesis of Indeterminate Potential (CHIP). In this common, age-related condition, mutated blood stem cells in the bone marrow multiply more efficiently than normal ones. A person with CHIP has a population of these mutated blood cells but does not have blood cancer. It is estimated that about 10% of people over 70 have a form of CHIP.
While CHIP is not a disease, its presence increases the risk for other health problems, primarily certain blood and bone marrow cancers. These include myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). Approximately 30% of people with these myeloid cancers have a TET2 mutation.
Beyond cancer, CHIP is also associated with an increased risk for cardiovascular diseases like heart attacks and strokes. This connection is driven by inflammation, as the mutated blood cells can contribute to inflammatory processes within blood vessels. This can accelerate the development of atherosclerosis (hardening of the arteries).
Diagnosis and Detection
The discovery of a TET2 mutation often begins with routine blood work. A complete blood count (CBC) may show abnormalities, such as low red blood cell counts (anemia), low platelet counts, or unusual white blood cells. These findings are not a diagnosis but prompt further investigation.
To confirm a TET2 mutation, specialized genetic testing is required using a technology called next-generation sequencing (NGS). An NGS panel analyzes many genes from a single blood sample to look for specific mutations associated with blood disorders, including TET2.
If a blood cancer like MDS or leukemia is suspected, a doctor may recommend a bone marrow aspirate and biopsy. This procedure involves taking a small sample of bone marrow fluid and tissue. Pathologists examine these samples to assess the blood-forming cells and can perform genetic tests on them.
Management and Treatment Approaches
Managing a TET2 mutation depends on whether it exists as CHIP or has progressed to a diagnosed blood cancer. For individuals with CHIP and no signs of cancer, the approach is “active surveillance.” This involves regular blood tests to monitor blood cell counts for any changes that might suggest progression.
A primary focus for managing CHIP is controlling cardiovascular disease risks. Management includes lifestyle modifications and medical interventions to lower the risk of heart attacks and strokes. This involves:
- Monitoring and treating high blood pressure
- Managing cholesterol levels
- Maintaining a healthy weight
- Controlling blood sugar
If the mutation is found with a cancer like MDS or AML, treatment targets the cancer itself, not the mutation. For these cancers, a class of drugs called hypomethylating agents may be used to help restore more normal cell function. Other treatments can include chemotherapy or a stem cell transplant.