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Updated: Jul 25, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
A distinct molecular mutational profile and its clinical impact in essential thrombocythemia and primary
Uzma Zaidi1, Gul Sufaida2, Munazza Rashid2
1Department of Clinical Hematology, National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, Pakistan. uzaidi26@gmail.com.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
This study analyzed myeloproliferative neoplasms in Pakistan, finding a distinct molecular profile and lower leukaemic transformation risk in Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) patients compared to other Asian populations.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Classical myeloproliferative neoplasms (MPNs), including Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF), are chronic conditions with a risk of leukaemic transformation.
- Accurate diagnosis and management are crucial for patient outcomes.
Purpose of the Study:
- To investigate the mutational profile, clinical characteristics, and outcomes of ET and PMF patients in the Pakistani population.
- To compare these findings with international data, particularly from other Asian countries.
Main Methods:
- A prospective observational study was conducted from 2012 to 2017 at the National Institute of Blood Diseases (NIBD).
- Patients were diagnosed and risk-stratified according to international guidelines.
- Treatment response was assessed using International Working Group (IWG) criteria.
Main Results:
- The study analyzed 137 patients: 75 with ET and 62 with PMF.
- JAK2 mutations were found in 37.2%, CALR in 29.9%, and 12.4% were triple-negative; no MPL mutations were observed.
- Overall survival (OS) for ET and PMF was 92.5% and 86.0%, respectively. Leukaemic transformation occurred in 6.5% of MF patients, more frequently with JAK2 mutations. In PMF, triple-negative patients had the shortest OS.
Conclusions:
- The Pakistani population exhibits a different spectrum of molecular mutations in ET and PMF compared to other Asian countries.
- The risk of leukaemic transformation in ET and PMF appears lower in this population.
- Further large-scale studies with extended follow-up are needed to elucidate the factors behind these phenotypic and genotypic differences.
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