Mutational landscape of classical myeloproliferative neoplasms in the Western Cape Province, South Africa.

BACKGROUND: The classical myeloproliferative neoplasms (MPNs) are driven by somatic variants in Janus kinase 2 (JAK2), calreticulin (CALR) and thrombopoietin receptor (MPL) genes. The heterogeneity in mutational frequency of JAK2, CALR, MPL and triple-negative MPNs between regions indicates that epidemiological studies in sub-Saharan Africa are required. OBJECTIVE: The aim of this study was to describe the genetic variants seen in MPNs at a South African tertiary hospital. METHODS: A retrospective study was conducted at Tygerberg Hospital, Western Cape Province, South Africa. Patients investigated for a classical MPN driver variant (polycythaemia vera [PV], primary myelofibrosis [PMF] and essential thrombocythaemia [ET]) from 2009 to 2020 were included in the study. The associated MPN diagnosis was sought from full blood count and bone marrow reports. Janus kinase 2-positive and -negative groups were compared for each MPN using a two-tailed independent samples t-test. RESULTS: There were 128 patients diagnosed with an MPN over the 12-year study period. Polycythaemia vera was the most prevalent (38%), followed by PMF (33%), essential thrombocythaemia (20%), and MPN unclassifiable (9%). The most frequent variant was JAK2 p.V617F (78%) followed by CALR variants (8%). No MPL variants were detected among the patients tested. In PMF, patients with JAK2 p.V617F variants were older (mean age 65 years vs 58 years, p = 0.048) and had a higher haemoglobin (10.6 g/dL vs 8.1 g/dL, p = 0.013) at diagnosis when compared to patients without JAK2 p.V617F. CONCLUSION: These data suggest that there are differences with regard to MPN epidemiology and variant frequency in South Africa, and further clinical studies are required to fully characterise MPNs in the South African context. WHAT THIS STUDY ADDS: This retrospective study expanded the profiling of MPNs and driver variants of MPNs in a South African population. Primary myelofibrosis made up a higher percentage of MPN cases than reported in international studies. In addition, in PMF and essential thrombocythaemia, JAK2 p.V617F was more common and CALR variants were less common than reported internationally, while MPL variants were not detected.