Mutational landscape of classical myeloproliferative neoplasms in the Western Cape Province, South Africa.
Key claim: In a South African tertiary-hospital cohort of classical MPNs, PMF made up a larger share of cases than in international series, JAK2 p.V617F predominated, CALR mutations were uncommon, and no MPL mutations were detected.
Abstract
BACKGROUND: The classical myeloproliferative neoplasms (MPNs) are driven by somatic variants in(),() and() genes. The heterogeneity in mutational frequency ofand 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.-positive and -negative groups were compared for each MPN using a two-tailed independent samples-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 wasp.V617F (78%) followed byvariants (8%). Novariants were detected among the patients tested. In PMF, patients withp.V617F variants were older (mean age 65 years vs 58 years,= 0.048) and had a higher haemoglobin (10.6 g/dL vs 8.1 g/dL,= 0.013) at diagnosis when compared to patients withoutp.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,p.V617F was more common andvariants were less common than reported internationally, whilevariants were not detected.
Why this matters
Most MPN subtype epidemiology and driver-mutation frequencies derive from European and North American series; this Western Cape South African cohort is the first substantial classical-MPN landscape from the region and shows a distinctly different pattern — more PMF, JAK2 V617F dominance, uncommon CALR, and absent MPL. That divergence has direct implications for regional risk stratification, transformation-risk modeling, and applicability of CALR- and MPL-directed therapies now entering the pipeline. It also raises the question of whether ancestry, referral patterns, or environmental exposures underpin these differences in MPN subtype natural history.