Classical 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. This 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. Of 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. This 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.

中文翻译：

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原发性血小板增多症和原发性骨髓纤维化患者的独特分子突变谱及其临床影响


包括 ET 和 PMF 在内的经典 MPN 具有慢性病程并有可能转化为白血病。必须及时诊断，以确保适当的管理和积极的结果。本研究的目的是确定巴基斯坦人群中 ET 和 PMF 患者的突变谱、临床特征和结果。这是 NIBD 于 2012 年至 2017 年间进行的一项前瞻性观察性研究。根据国际建议对患者进行诊断和风险分层。根据 IWG 标准评估治疗反应。在分析的总共 137 名患者中，75 名是 ET，62 名是 PMF。 JAK2 阳性 51 例（37.2%），CALR 41 例（29.9%），三阴性 17 例（12.4%）。本研究中没有患者呈 MPL 阳性。中位随访 12 个月时，ET 和 PMF 患者的总生存率分别为 92.5% 和 86.0%，无白血病生存率分别为 100% 和 91.6%。 6.5% 的 MF 患者发生白血病转化；其中，JAK2突变最为常见。分子突变不影响 ET 中的 OS，而在 PMF 中，与 JAK2 和 CALR 阳性患者组相比，三阴性 PMF 组中的 OS 最短。这项研究显示，与其他亚洲国家相比，巴基斯坦人群中 ET 和 PMF 患者的分子突变谱不同。同样，在我们的患者群体中，ET 和 PMF 发生白血病转化的风险相对较低。需要在大规模研究中对导致这些表型和基因型差异的因素进行分析，并对患者进行更长时间的随访。