Essential Thrombocythemia (ET) is a chronic type of blood cancer, classified as a myeloproliferative neoplasm (MPN), characterized by the excessive production of blood-clotting cells called platelets. This overproduction originates in the bone marrow. Many people diagnosed with ET wonder if they inherited the condition or if they might pass it on. Essential Thrombocythemia is overwhelmingly not a hereditary disease, but understanding the difference between acquired and inherited risk is important.
Defining Essential Thrombocythemia
Essential Thrombocythemia is defined by a persistently elevated platelet count, typically exceeding 450,000 per microliter of blood, for which no other cause can be identified. Platelets are normally responsible for stopping bleeding by forming blood clots. In ET, the bone marrow’s stem cells that produce platelets undergo an abnormal, uncontrolled proliferation.
The excessive number of platelets circulating in the bloodstream can lead to two main health concerns: abnormal clotting or bleeding. Clotting events, known as thrombosis, are the most common serious complication, potentially resulting in a stroke, heart attack, or deep vein thrombosis. Paradoxically, some individuals with extremely high platelet counts may experience bleeding issues, such as nosebleeds, due to a clotting protein deficiency.
ET is considered a chronic blood cancer because it involves the clonal expansion of an abnormal blood stem cell population. The term “essential” indicates that the high platelet count is due to a primary bone marrow disorder rather than a reaction to another underlying condition, such as infection or iron deficiency. Management of ET focuses on reducing the risk of vascular complications.
Acquired vs. Inherited Risk
Essential Thrombocythemia is an acquired condition. Over 90% of all ET diagnoses result from a genetic change that occurs in a single blood stem cell after conception, known as a somatic mutation. This mutation is present only in the affected blood cells and is not found in the germline (sperm or egg cells responsible for inheritance).
The distinction between an acquired somatic mutation and an inherited germline mutation is important. A somatic change cannot be passed from parent to child because it did not exist in the DNA of the original reproductive cells. Therefore, most people with ET have no family history of the disease.
A small fraction of cases, estimated to be less than 5%, are classified as familial MPNs, where multiple family members are affected. Even in these rare familial clusters, the pattern of inheritance is often complex and does not follow the simple rules of Mendelian inheritance. These cases suggest a genetic predisposition that increases the likelihood of developing the disease, rather than the direct inheritance of the cancer itself.
The Role of Specific Gene Mutations
Essential Thrombocythemia is tied to specific acquired genetic changes. Three main driver mutations, all somatic in nature, are responsible for nearly 80% of all ET cases. The most common is a mutation in the JAK2 gene, specifically the V617F variant, found in approximately 50% to 60% of patients.
The JAK2 gene provides instructions for a protein that helps control the production of blood cells in the bone marrow. The V617F mutation causes this protein to be constantly switched “on,” leading to the uncontrolled growth of megakaryocytes (the platelet-producing cells). This mechanism explains the overproduction of platelets characteristic of ET.
Other major somatic mutations include those in the CALR gene (found in 20% to 25% of cases) and the MPL gene (found in 3% to 7% of cases). The CALR and MPL mutations also lead to the activation of the same signaling pathway as JAK2, resulting in the clonal proliferation of abnormal blood cells. Since these mutations are limited to the bone marrow cells, they confirm that the cancer is acquired.
Understanding Familial Risk and Screening
Having a first-degree relative (a parent, sibling, or child) with any myeloproliferative neoplasm slightly elevates an individual’s risk compared to the general population. This small increase in risk is likely due to inherited predisposition genes. These genes do not cause the disease directly, but they make the bone marrow stem cells more vulnerable to acquiring a somatic mutation later in life.
In rare instances of familial ET, the inherited genetic changes are often found in different genes than the common somatic drivers. For example, germline mutations in the THPO gene, which regulates platelet production, or non-V617F mutations in JAK2 or MPL, have been implicated in hereditary forms of thrombocytosis. These germline variants are present in all cells of the body.
Formal screening for family members of an ET patient is not routinely recommended unless there is a strong family history of multiple affected individuals. Awareness and close monitoring by a physician are recommended. If a familial predisposition is suspected, genetic counseling can be beneficial to discuss specific risks and the potential for targeted genetic testing.