These all have high incidence of the JAK-2 kinase mutation which causes over expression of tyrosine kinase
Disorder |
Characteristics |
Clinical Features |
Diagnostic Tests |
Treatment |
Chronic Myeloid Leukaemia (CML) |
- Characterized by the overproduction of mature granulocytes (neutrophils, eosinophils, and basophils).
- Associated with the Philadelphia chromosome (t(9;22) translocation), leading to the BCR-ABL fusion gene.
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- Fatigue, weight loss, night sweats.
- Splenomegaly, often significant.
- Leukocytosis, typically marked.
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- Complete Blood Count (CBC): Elevated white blood cell count, often with a left shift.
- Bone Marrow Biopsy: Hypercellularity with granulocytic hyperplasia.
- Genetic Testing: Presence of the Philadelphia chromosome and BCR-ABL gene by PCR or FISH.
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- Tyrosine Kinase Inhibitors (TKIs): Imatinib is the first-line treatment.
- Hematopoietic Stem Cell Transplant: Considered in cases of resistance or progression.
- Monitoring: Regular monitoring of BCR-ABL levels to assess treatment response.
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Polycythemia Vera (PV) |
- Characterized by the overproduction of red blood cells.
- Often associated with the JAK2 V617F mutation.
- Increased blood viscosity leading to a higher risk of thrombosis.
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- Headache, dizziness, and visual disturbances.
- Pruritus, especially after a hot bath (aquagenic pruritus).
- Splenomegaly and erythromelalgia (burning pain in hands or feet with erythema).
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- CBC: Elevated haemoglobin and hematocrit levels.
- Erythropoietin (EPO) Levels: Low serum EPO levels.
- JAK2 Mutation Testing: Presence of JAK2 V617F mutation confirms diagnosis.
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- Phlebotomy: Regular removal of blood to maintain hematocrit below 45%.
- Aspirin: Low-dose aspirin to reduce the risk of thrombosis.
- Hydroxyurea: For high-risk patients or those with symptomatic splenomegaly.
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Essential Thrombocythemia (ET) |
- Characterized by the overproduction of platelets.
- Often associated with JAK2, CALR, or MPL mutations.
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- Thrombosis or bleeding complications.
- Headaches, dizziness, and visual disturbances.
- Erythromelalgia.
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- CBC: Elevated platelet count.
- Bone Marrow Biopsy: Increased megakaryocytes.
- JAK2, CALR, MPL Mutation Testing: Genetic testing for mutations.
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- Aspirin: Low-dose aspirin for patients at risk of thrombosis.
- Hydroxyurea: For high-risk patients to reduce platelet count.
- Anagrelide: Alternative to hydroxyurea for platelet control.
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Primary Myelofibrosis (PMF) |
- Characterized by the replacement of bone marrow with fibrous tissue.
- Often associated with JAK2, CALR, or MPL mutations.
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- Fatigue, weight loss, and night sweats.
- Splenomegaly, often massive.
- Anaemia, bleeding, and infections due to bone marrow failure.
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- CBC: Anaemia, variable white blood cell and platelet counts.
- Bone Marrow Biopsy: Fibrosis with decreased hematopoietic cells.
- Genetic Testing: JAK2, CALR, or MPL mutations.
- Peripheral Blood Smear: Teardrop-shaped red cells (dacrocytes) and leukoerythroblastosis.
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- JAK Inhibitors: Ruxolitinib for symptom relief and spleen size reduction.
- Supportive Care: Blood transfusions, iron chelation for anaemia.
- Stem Cell Transplant: The only potential cure, reserved for younger patients with high-risk disease.
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