Background: MPNs are clonal haemopoietic disorders that are characterized by excessive proliferation of one or more of blood lineages. MPNs include PV, ET and PMF which are associated by the presence of JAK2 V617F mutation in about 90% of PV and 50% of ET and PMF. The molecular workup of JAK2 & related gene mutations were included in WHO 2008 as one major criterion for the diagnosis of Ph- MPNs. Aim: To genetically characterize MPN patients (pts) in Qatar according to the latest(WHO 2008) criteria using molecular studies for JAK2 V617F mutation, JAK2 exons 12-15 & MPL (S505N & W515 L/K) mutations. Methods: Blood samples were collected from suspected MPN cases & DNA was extracted. Allelic discrimination assays were used to evaluate point mutations causing JAK2 V617F & MPL (W515 L/K) mutations. JAK2 Exon 12 was analyzed using High Resolution Melting Curve (HRM) assay & Sanger Sequencing. In some cases the entire MPL exon 10 & exons 12-15 was studied by RNA extraction followed by cDNA synthesis, amplification & sequencing. Results: 400 patients were classified into PV, ET and PM. Out of 180 PV, 97% of cases were positive for the JAK2 V617F mutation and 3% of cases were negative for other mutations. Out of 200 ET, 48% of cases were positive for JAK2 V617F, one had MPL S505N mutation and 50% of cases were negative for other mutations. Out of 20 PMF, 33% of cases were positive for JAK2 V617F and one unclassified case was characterized by DVT had JAK2 exon 13 mutation (R564L). Conclusion: This study used novel molecular approaches to confirm the diagnosis of MPNs cases in Qatar. The observed patterns of mutations were found to be similar to the international data. In our cohorts of patients, JAK2 V617F mutation was found to be present in almost every patient with PV, nearly 50% of ET patients and less than 50% of PMF patients due to the low number of PMF patients in this study. Our original findings show the presence of MPL S505N mutation in one ET patient which was reported both as an inherited or acquired mutation in very rare cases of ET and R564L mutation in one unclassified MPNs case. An ET patient with MPL S505N progressed to AML. The impact of R564L mutation found in 1 atypical case is still unknown & needs further investigation. We report for the first time the presence of most frequent mutations found in MPNs patients in Qatar. This study is preliminary before further molecular investigations to explore & identify mutations in other candidate genes.


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