From the Guidelines
Janus Kinase (JAK) inhibitors have a significant relationship with conditions such as anemia, neutropenia, and lymphopenia, particularly in the context of myeloproliferative neoplasms (MPNs).
JAK Inhibitors and MPNs
- JAK2 mutations are found in over 90% of patients with polycythemia vera (PV) and approximately 60% of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) 1.
- Ruxolitinib, a JAK inhibitor, has been shown to have symptomatic benefits in myelofibrosis (MF), but can also cause anemia and thrombocytopenia as on-target effects 1.
Anemia and JAK Inhibitors
- Anemia is a hallmark of MF and can be exacerbated by JAK inhibitors such as ruxolitinib, which can cause dose-limiting anemia and thrombocytopenia 1.
- Combinations of ruxolitinib with antianemia medications, such as danazol, erythropoiesis-stimulating agents (ESAs), and immunomodulatory drugs (IMiDs), are being explored to alleviate anemia in MF patients 1.
Neutropenia and Lymphopenia
- While the provided evidence does not directly address the relationship between JAK inhibitors and neutropenia or lymphopenia, it is known that JAK inhibitors can affect blood cell counts, including neutrophils and lymphocytes.
- However, the evidence suggests that JAK inhibitors such as ruxolitinib are primarily associated with anemia and thrombocytopenia, rather than neutropenia or lymphopenia 1.
From the Research
Relationships between JAK1, JAK2, and JAK3 and Hematological Conditions
- JAK1, JAK2, and JAK3 are non-receptor protein tyrosine kinases that play crucial roles in cytokine receptor signaling in blood formation and immune responses 2.
- Mutations and translocations in the JAK genes leading to constitutively active JAK proteins are associated with various hematopoietic malignancies, including myeloproliferative disorders, acute lymphoblastic leukemia, and acute myeloid leukemia 2, 3.
- JAK2 is important in myeloid cell proliferation and differentiation, while JAK3 is important in lymphoid cell proliferation and differentiation 3.
- Germline loss-of-function mutations of JAK3 can lead to severe combined immunodeficiency, which is often characterized by conditions such as anemia, neutropenia, and lymphopenia 3, 4.
JAK Inhibitors and Their Therapeutic Applications
- JAK inhibitors have been developed and are being tested in humans with myeloproliferative neoplasms, such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis 3, 5.
- JAK inhibitors have also been approved for the treatment of rheumatoid and psoriatic arthritis, atopic dermatitis, ulcerative colitis, graft-versus-host disease, alopecia areata, ankylosing spondylitis, and COVID-19 4.
- Dual-target JAK inhibitors, which combine inhibition of JAK and other oncogenic targets, have shown significant advantage and superiority over single-target inhibitors in the treatment of immune-related diseases and cancers 6.
JAK Mutations and Their Associations with Hematological Conditions
- Somatic gain-of-function JAK mutations, particularly JAK2 V617F, are associated with myeloproliferative neoplasms and other hematologic malignancies 3, 4.
- JAK2 copy-number loss is associated with immune checkpoint inhibitor resistance 4.
- Germline mutations and polymorphisms of JAK family members correlate with specific diseases, such as systemic lupus erythematosus, severe combined immunodeficiency, and hereditary thrombocytosis 4.