Polycythemia vera is a chronic clonal myeloproliferative disorder characterized by increase in the number of red blood cells, total blood volume, and usually by leukocytosis, thrombocytosis, and splenomegaly.
Bone marrow is typically hypercellular and exibits hyperplasia of myeloid, erythroid and megakaryocyte lineages.
Polycythemia rubra vera
Polycythemia with chronic cyanosis
Vaquez, in 1892 first described persistent polycthemia.
Osler, in 1903 and 1908 clarified clinical picture of the disease.
Turk, in 1904, called attention to the occurrence of leukocytosis with erythrocytosis.
Revised WHO criteria for PCV
Hgb >18.5 g/dl in men, 16.5 g/dL in women or evidence of increased red cell volume.
Presence of JAK2 V617F mutation
Hypercellular bone marrow biopsy with prominent erythroid, granulocytic, and megakaryocytic hyperplasia.
Serum erythropoietin level below normal reference range.
Endogenous erythroid colony formation in vitro
Using vitro culture techniques, there is formation of erythroid colonies in absence of added erythropoietin
Diagnosis requires presence of both major criteria and 1 minor or first major and 2 minor criteria.
Of the various MPDs, there are the four common disorders, recognized as chronic myelogenous leukemia (CML), with its characteristic 9;22 translocation and BCR / ABL fusion protein, and other three non-CML MPDs – Polycythemia Vera, Essential Thrombocythemia and Chronic Idiopathic Myelofibrosis.
These common non-CML MPDs (PV, ET, CIMF) share a high incidence of the acquired point mutation in the JAK2 kinase, a cytoplasmic tyrosine kinase, important in hematopoetic cell proliferation.
The Janus kinase 2 gene ( JAK2 ) codes for a tyrosine kinase (JAK2) which is a transmembane receptors, important for signal transduction in hematopoietic cells.
Binding of JAK2 receptor by extracellular ligand causes receptor multimerization and activation by transphosphorylation.
Activated JAK2 then phosphorylates the cytoplasmic portion of the receptor and a cytoplasmic transcription factor, STAT5 (Signal Transducers and Activation of Transcription).
Phosphorylated STAT5 then translocate into the nucleus and initiate gene transcription, ultimately responsible for cell growth and differentiation.
There is gain of function mutation on the short arm of chromosome 9, in which valine at position 617 of the Janus kinase 2 gene is replaced by phenylalanine (JAK2 V617F).
Mutation occurs in pseudokinase which is normally a negative regulator of kinase activity, resulting in continuously activated tyrosine kinase.
Involvement of Janus Kinases in Cytokine Signal Transduction (Panel A) and Structural Map of Janus Kinase 2 (Panel B)
Mutation is exclusive to disorders of myeloid lineage and not observed in lymphoid neoplasms or solid tumors.
This mutation appears to be present in upto 95% of PV patients. However, a significant proportion of patients with essential thrombocytosis and myelofibrosis also have the JAK2 mutation (about 30% – 50%).
Other cytogenetic abnormalities associated with PV are -