RESUMO
BACKGROUND: Mutations in JAK2/STAT5 proliferation pathway genes are key in the diagnosis of myeloproliferative neoplasms (MPNBCR/ABLneg), with JAK2V617F being found in 50-97% of MPNBCR/ABLneg subtypes. Low JAK2V617F positivity at our facility suggested that our South African MPNBCR/ABLneg population may have a different mutational landscape. OBJECTIVES: We aimed to determine the JAK2/STAT5 mutation frequencies associated with our local MPNBCR/ABLneg population, thus determining the relevance of these molecular tests in this group. We also investigated the haematopathological relevance of each test request, to assess testing practises. METHOD: This study involved the retrospective audit of 886 patients for whom JAK2V617F mutation testing had been requested for a suspected MPN diagnosis. FBC indices, erythropoietin levels and bone marrow biopsy results were used to classify the patients. JAK2V617F negative patient DNA was tested for calreticulin (CALR) exon9, myeloproliferative leukaemia protein (MPL) codon515 and JAK2 exon12 mutations. RESULTS: Only 23% of the patients demonstrated JAK2V617F positivity, with an additional 29 cases of CALR/MPL mutations being detected. Mutations were only detected in patients with abnormal FBC indices, as expected, yet 37% of the test requests were not associated with abnormal parameters at the time of testing. Mutation frequencies were as follows: Polycythaemia Vera: 97% JAK2V617F/3% (JAK2, CALR, MPL) triple negative; Essential thrombocythemia: 72% JAK2V617F/23%CALR/5%triple negative; Primary Myelofibrosis: 78%JAK2V617F/16%CALR/6%triple negative. CONCLUSION: Our study demonstrated that our MPNBCR/ABLneg patients have a similar genetic landscape to other MPN populations, with >93% being able to be diagnosed by testing for the JAK2V617F and CALR exon9 mutations alone. Adoption of the WHO 2016 guidelines is recommended to guide testing practices.