A distinct molecular mutational profile and its clinical impact in essential thrombocythemia and primary myelofibrosis patients

Uzma Zaidi,Saima Munzir,Sidra Maqsood,Samina Naz Mukry,Rifat Zubair Ahmed Khan,Gul Sufaida,Munazza Rashid,Tahir Sultan Shamsi,Bushra Kaleem,Munira Borhany

doi:10.1186/s12885-020-6700-3

Uzma Zaidi, Saima Munzir + Show 8 more

Open Access

https://doi.org/10.1186/s12885-020-6700-3

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Abstract

BackgroundClassical MPNs including ET and PMF have a chronic course and potential for leukaemic transformation. Timely diagnosis is obligatory to ensure appropriate management and positive outcomes. The aim of this study was to determine the mutational profile, clinical characteristics and outcome of ET and PMF patients in Pakistani population.MethodsThis was a prospective observational study conducted between 2012 and 2017 at NIBD. Patients were diagnosed and risk stratified according to international recommendations. Response to treatment was assessed by IWG criteria.ResultsOf the total 137 patients analysed, 75 were ET and 62 were PMF. JAK2 positivity was seen in 51 cases (37.2%), CALR in 41 cases (29.9%), while triple-negative in 17 (12.4%) cases. None of the patients in the present study were MPL positive. Overall survival for patients with ET and PMF was 92.5 and 86.0% respectively and leukaemia free survival was 100 and 91.6% respectively, at a median follow-up of 12 months. Leukaemic transformation occurred in 6.5% of MF patients; among them, JAK2 mutation was frequently found. Molecular mutations did not influence the OS in ET whereas in PMF, OS was shortest in the triple-negative PMF group as compared to the JAK2 and CALR positive patient groups.ConclusionThis study shows a different spectrum of molecular mutations in ET and PMF patients in Pakistani population as compared to other Asian countries. Similarly, the risk of leukaemic transformation in ET and PMF is relatively lower in our population of patients. The factors responsible for these phenotypic and genotypic differences need to be analysed in large scale studies with longer follow-up of patients.

Highlights

Classical myeloproliferative neoplasms (MPNs) including Essential thrombocythemia (ET) and Primary myelofibrosis (PMF) have a chronic course and potential for leukaemic transformation
The most recent revision of the classification of MPN published by the World Health Organization (WHO) has incorporated the presence of CALR and Thrombopoietin receptor gene (MPL) mutations in the diagnostic criteria of PMF and ET based on the current evidences [5]
Frequencies of molecular and cytogenetic mutations A total of 137 patients were analysed in this study, 75 patients were diagnosed with ET and 62 patients were diagnosed with PMF

Summary

Introduction

Classical MPNs including ET and PMF have a chronic course and potential for leukaemic transformation. The incidence of the classical MPNs reported worldwide is approximately 0.5–6/100,000 per year It is considered a disease of the elderly with peak incidence occurring in the 5th to 6th decades of life [1, 2]. The latest advancements in the molecular pathogenesis of classical MPN have revealed that each subtype of MPN carries a specific driver mutation including JAK2, CALR and MPL or somatic mutations in TET2, ASXL1, IDH, IKZF1, EZH2, DNMT3A, TP53, SF3B1, SRSF2, U2AF1 or other mutations [4]. CALR mutations which are typically insertions or deletions and involve exon 9 have been reported in 60–90% of PMF and ET patients with unmutated JAK2 or MPL [6]. It is generally believed that driver mutations are crucial for the MPN phenotype whereas the other mutations are associated with disease progression and leukaemic transformation [8]

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