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Updated: Jun 14, 2026
Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
The analysis of JAK2 and MPL mutations and JAK2 single nucleotide polymorphisms in MPN patients by MassARRAY assay
1Department of Haematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, China.
Abstract:
Recent studies have shown that JAK2 V617F, MPL W515L/K and JAK2 exon 12 mutations underlie the major molecular pathogenesis of myeloproliferative disorders (MPN). Allele-Specific Polymerase Chain Reaction (AS-PCR), direct sequencing and MassARRAY assay were used to ascertain the real prevalence of these mutations and the influence of genetic susceptibility in Chinese MPN patients. The positive rate of JAK2 V617F in polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) was 82.0%, 36.6% and 51.1% respectively. One ET patient and two PMF patients harboured the MPL W515L mutation and three PV patients harboured JAK2 exon 12 mutations. All of these patients were confirmed as JAK2 V617F negative. Clinical data demonstrated that PV patients with JAK2 exon 12 mutations were younger, had higher haemoglobin levels and white blood cell counts than PV patients with JAK2 V617F. In addition, through analysis of 4 polymorphic loci of JAK2 gene, no significant difference of distribution frequency was found among PV, ET and PMF patients. Distribution frequency of haplotype also was not significantly different among PV, ET and PMF patients. We conclude that JAK2 V617F is a major molecular pathogenesis in Chinese MPN patients. MPL W515L mutation and JAK2 exon 12 mutations can also be found in JAK2 V617F negative MPN patients.
Insights
JAK2 V617F mutations are the primary cause of myeloproliferative disorders (MPN) in Chinese patients. Other mutations, like MPL W515L and JAK2 exon 12, are found in JAK2 V617F-negative MPN cases.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Myeloproliferative disorders (MPN) are a group of clonal hematopoietic stem cell malignancies.
- Specific mutations in JAK2, MPL, and CALR genes are known drivers of MPN pathogenesis.
- Understanding the prevalence and clinical significance of these mutations in diverse populations is crucial.
Purpose of the Study:
- To determine the prevalence of JAK2 V617F, MPL W515L/K, and JAK2 exon 12 mutations in Chinese MPN patients.
- To investigate the clinical characteristics of MPN patients with different mutational profiles.
- To explore the influence of genetic susceptibility on MPN development in this population.
Main Methods:
- Allele-Specific Polymerase Chain Reaction (AS-PCR) was employed for mutation detection.
- Direct sequencing and MassARRAY assay were utilized for precise mutation ascertainment.
- Analysis included 4 polymorphic loci of the JAK2 gene to assess genetic susceptibility.
Main Results:
- JAK2 V617F was detected in 82.0% of Polycythaemia Vera (PV), 36.6% of Essential Thrombocythaemia (ET), and 51.1% of Primary Myelofibrosis (PMF) patients.
- MPL W515L mutations were identified in one ET and two PMF patients (JAK2 V617F negative).
- JAK2 exon 12 mutations were found in three PV patients (JAK2 V617F negative), who presented with younger age and higher hemoglobin/WBC counts compared to JAK2 V617F positive PV patients.
- No significant differences in the distribution frequency of JAK2 polymorphic loci or haplotypes were observed among PV, ET, and PMF patients.
Conclusions:
- JAK2 V617F is the predominant molecular driver in Chinese MPN patients.
- MPL W515L and JAK2 exon 12 mutations represent important alternative molecular events in JAK2 V617F-negative MPN.
- Genetic susceptibility, assessed by JAK2 polymorphic loci and haplotypes, did not significantly influence MPN subtypes in this cohort.
