What is the Janus Kinase 2 (JAK2) mutation associated with?

From the Guidelines

JAK2 mutations are primarily associated with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The most common JAK2 mutation, V617F, is found in approximately 95% of patients with polycythemia vera, 50-60% of patients with essential thrombocythemia, and 50-60% of patients with primary myelofibrosis, as reported in a study published in the Journal of Clinical Oncology 1. These disorders involve overproduction of red blood cells, platelets, or fibrosis of the bone marrow, respectively.

Key Associations

• Polycythemia vera (PV): characterized by overproduction of red blood cells
• Essential thrombocythemia (ET): characterized by overproduction of platelets
• Primary myelofibrosis (PMF): characterized by fibrosis of the bone marrow JAK2 mutations can also occur in other hematologic conditions like refractory anemia with ring sideroblasts and thrombocytosis, as noted in a study published in Blood 1. The mutation affects the Janus kinase 2 protein, which plays a crucial role in blood cell production by mediating signals from growth factor receptors. When mutated, JAK2 becomes constitutively active, leading to uncontrolled cell proliferation independent of growth factor stimulation. This dysregulation results in the overproduction of blood cells characteristic of MPNs. Testing for JAK2 mutations is an important diagnostic tool for patients with suspected myeloproliferative disorders.

From the FDA Drug Label

Pacritinib is an oral kinase inhibitor with activity against wild type Janus associated kinase 2 (JAK2), mutant JAK2V617F, FMS-like tyrosine kinase 3 (FLT3), and interleukin 1 receptor associated kinase-1 (IRAK1) which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function Momelotinib is an inhibitor of wild type Janus Kinase 1 and 2 (JAK1/JAK2) and mutant JAK2V617F, which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function.

The JAK2 mutation is associated with myeloproliferative neoplasms, such as myelofibrosis (MF), which is characterized by constitutive activation and dysregulated JAK signaling. This leads to inflammation and hyperactivation of ACVR1, resulting in increased red blood cell production.

• Key points:
  • JAK2 mutation is associated with myeloproliferative neoplasms
  • Myelofibrosis (MF) is a type of myeloproliferative neoplasm
  • JAK2 mutation leads to constitutive activation and dysregulated JAK signaling
  • This results in inflammation and hyperactivation of ACVR1
  • Ultimately leading to increased red blood cell production 2 3

From the Research

JAK2 Mutation Association

The JAK2 mutation is associated with several myeloproliferative neoplasms, including:

• Essential thrombocythemia (ET) 4, 5, 6, 7
• Polycythemia vera (PV) 4, 5, 6, 8, 7
• Primary myelofibrosis (PMF) 4, 5, 6, 8, 7
• Acute myeloid leukemia (AML) 8

Clinical Implications

The presence of a JAK2 mutation has significant clinical implications, including:

• Increased risk of thrombosis 4, 5, 6
• Leukemic transformation 4, 8
• Disease transformation into myelofibrosis or acute myeloid leukemia 4
• Abnormal karyotype 4, 7

Diagnostic and Therapeutic Considerations

The JAK2 mutation is a key factor in the diagnosis and treatment of myeloproliferative neoplasms, with:

• JAK2 mutation detection useful in diagnosis 6, 7
• JAK-STAT pathway as a target for drug development 6, 8
• Anti-JAK2 small molecule drugs showing therapeutic potential 6, 8