The Janus Kinase 2 (JAK2) test is a specialized molecular diagnostic tool used to examine the JAK2 gene for acquired genetic alterations. These mutations cause the JAK2 protein to become constantly active, leading to the uncontrolled production of blood cells in the bone marrow. This genetic analysis is a standard component in the diagnostic workup for conditions that affect blood cell counts, helping physicians classify the specific disorder and plan management.
Clinical Context and Purpose
The JAK2 test is ordered when a physician suspects a Myeloproliferative Neoplasm (MPN), a blood cancer characterized by the overproduction of red blood cells, white blood cells, or platelets. This suspicion often follows routine blood work, such as a Complete Blood Count (CBC), showing abnormal cell counts. Confirming the presence of a JAK2 mutation is a major diagnostic criterion for most MPNs.
The JAK2 gene provides instructions for making the JAK2 protein, an enzyme that acts as a signal relay within the cell. This protein is a key part of the JAK-STAT signaling pathway, which transmits chemical messages from growth factors to the nucleus. This pathway regulates the growth, division, and maturation of blood-forming stem cells in the bone marrow. The JAK2 protein controls the production of all types of blood cells, including red blood cells, white blood cells, and platelets.
When a JAK2 mutation occurs, the resulting protein is permanently “switched on,” sending continuous growth signals to the stem cells. This unregulated signaling causes the bone marrow to produce an excessive number of mature blood cells, causing MPNs. The specific diseases linked to this mutation are Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF).
Identifying a JAK2 mutation helps differentiate MPNs from other conditions, such as reactive cytosis. The test also guides therapeutic decisions, as certain medications, known as JAK inhibitors, target the hyperactive JAK2 protein. The specific mutation type and percentage of mutated cells influence the disease course and treatment plan.
The JAK2 Test Procedure
The JAK2 test uses a blood sample collected through standard venipuncture. The sample is usually collected in a lavender-top tube containing the anticoagulant EDTA. Patient preparation is generally not required, meaning the individual does not need to fast before the collection.
Once the sample reaches the laboratory, the process shifts to molecular analysis. The first step involves extracting DNA from the white blood cells present in the sample. This DNA contains the genetic code that the laboratory technicians will examine for mutations.
The extracted DNA is subjected to specialized techniques like Polymerase Chain Reaction (PCR) or Next-Generation Sequencing (NGS). These methods amplify a specific segment of the JAK2 gene to detect the mutation. The test looks for an acquired genetic change, which is a somatic mutation present only in the blood-forming cells.
Interpreting the Test Results
Interpreting JAK2 results involves looking for the presence, location, and quantity of the mutation. A “Positive” result indicates a JAK2 mutation was found, strongly supporting an MPN diagnosis. A “Negative” result does not rule out an MPN, as other gene mutations can cause these disorders.
The most common mutation is JAK2 V617F, found in exon 14 of the gene. It is present in the vast majority of Polycythemia Vera cases, and about half of Essential Thrombocythemia and Primary Myelofibrosis cases. This specific mutation involves a change of a single DNA base pair, resulting in the substitution of the amino acid valine with phenylalanine at position 617. The V617F variant is the primary molecular marker for these diseases.
JAK2 Exon 12 mutations are less common but are highly associated with Polycythemia Vera in patients who test negative for the V617F variant. These mutations occur in a different part of the gene and also lead to the same functional outcome: a constitutively active JAK2 protein that drives excessive red blood cell production. Patients with Exon 12 mutations often present primarily with an elevated red blood cell count.
Beyond identifying the mutation, the test may report the Variant Allele Frequency (VAF), also called the allele burden. This quantitative measurement indicates the percentage of DNA in the sample carrying the mutation. A higher allele burden is associated with a greater likelihood of Polycythemia Vera and can influence disease severity and the risk of progression. Monitoring the VAF tracks the patient’s response to therapy.