Implementation of the JAK2V617F mutation analysis in the pathway of suspected myeloproliferative neoplasms in Groote Schuur Hospital

Master Thesis


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University of Cape Town

We studied the implementation of JAK2 mutation analysis in conjunction with the World Health Organisation (WHO) guidelines in the pathway to MPN diagnosis in 279 patients presenting with one of three clinical scenarios: erythrocytosis, OR leukocytosis and/or thrombocytosis and/or splenomegaly; OR patients with thrombosis without cytoses. Patients were investigated for MPN and managed in the haematology clinic of Groote Schuur Hospital. We studied the association of clinical and laboratory variables with clonal vs non-clonal diagnoses. In 120/297 patients MPN was confirmed: Polycythemia vera (PV), (n=51, 100% JAK2 mutated); essential thrombocytosis, (n=41, 42% JAK2 mutated); primary myelofibrosis (n=28, 57% JAK2 mutated). The 2016 WHO haemoglobin/haematocrit thresholds in PV were validated. Idiopathic erythrocytosis (IE) found in 44 patients. Bone marrow histology, but not serum EPO level, was essential to differentiate between clonal and non-clonal erythrocytosis. Both PV and IE patients complied with the criteria of absolute erythrocytosis on peripheral blood, yet nuclear red cell mass identified critical differences between clonal and non-clonal erythrocytosis. No patient venesected for nonclonal erythropoiesis developed thrombocytosis. JAK2 mutation analysis applied with the WHO diagnostic algorithm efficiently differentiated true clonal myeloproliferation from reactive cytoses. Lifestyle and metabolic factors such as smoking and thrombosis were not associated with either clonal or non-clonal erythrocytosis, and were equally present in mutated and unmutated essential thrombocytosis.