<prompt> Which of the following is a major criteria for diagnosis of poycythemia vera:Presence of JAK-2 mutationLow Erythropoetin levelsHigh Leucocyte Alkaline Phosphatase TLAP scoreThrombocytosis  <response>: Answer is A Presence of JAK-2 mutation Presence of JAK-2 mutation is a Major criterion fir diagnosis of polycythemia Vera according to the proposed new WHO criteria for the diagnosis of Polycythemia Vera. Low Erythropoetin levels, Thrombocytosis and increased LAP scores are all minor criteria for diagnosis of polycythemia Vera. JAK-2 Mutation and Polycythemia Vera JAK-2 is a member of an evolutionarily well conserved, non receptor tyrosine kinase family and serves as the cognate tyrosine kinase for the erythropoietin receptors A mutation in the tyrosine kinase JAK-2 appears to have a central role in the pathogenesis of PV by causing constitutive activation of the kinase The presence of JAK -2 mutation thus allows for the exclusion of a reactive erythrocytosis. The 2001 WHO criteria for diagnosis of PV were however developed prior to the discovery of this impoant mutation and hence revised WHO criteria have been developed that include presence of JAK-2 mutation as a major criterion for diagnosis of PV Note : Although presence of JAK-2 mutation is a major criterion for diagnosis of PV, the presence of JAK-2 mutation alone is not diagnostic of PV. JAK-2 mutations may also be seen in other myeloproliferative disorders such as Essential Thrombocytosis ET and Chronic Idiopathic Myelojlbrosis CIMF. Various major and minor criteria used for the diagnosis of polvcythemia vera in various classification systems WHO criteria revised and old Polvcythemia vera study group criteria Major Minor JAK2 V617F mutation Thrombocytosis 400 x 109L Hemoglobin 18.5 gdL in men, 16.5 gdL in Leucocytosis WBC 12 x 109L women Increased leukocyte alkaline phosphatase LAP 100U Increased red blood cell mass Increased serum B12binders Splenomegaly B12 900 pgml; unbound B12 binding capacity 2200 pgml Clonal genetic abnormality other than Low serum erythroprotein levels. Philadelphia chromosome or BCRABL in marrow Panmyelosis with prominent erythoid and megakaryocytic Endogenous erythroid colony formation in vitro hyperplasia on bone marrow biopsy. Normal aerial 02 saturation 92 Revised WHO criteria Proposed for the diagnosis of Polycythemia vera Revised WHO criteria Proposed for the diagnosis of Polycythemia vera Major Criteria Hemoglobin 18.5 gdl in men, 16.5 gdl in women or evidenced on increased red cell volume Presence of JAK2 mutation Minor Criteria Hypercellular bone marrow biopsy with panmyelosis with prominent erythroid, granulocytic, and megakaryocytic hyperplasia Low serum erythropoietin level Endogenous erythroid colony formation in vitro. WHO Criteria Previous for the diagnosis of Plvcythemia vera Major Criteria Red blood cell mas 25 above mean normal predicted value, or Hb 18.5 gdl in men, 16.5 gdI in women. Splenomegaly on palpation Clonal genetic abnormality other than Philadelphia chromosome or BCRABL in marrow. Endogenous erythroid colony formation in vitro Minor Criteria Thrombocytosis 400 x 109L WBC 12 x 109L Panmyelosis with prominent erythroid and megakaryocytic hyperplasia on bone marrow biopsy. Low serum erythropoietin levels. WHO Criteria for the diagnosis of Plycythemia Vera Prior to the proposed new criterion 