Abstract
Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal hematological diseases involving abnormal myeloid stem cell proliferation. Understanding genetic mutations driving diseases promotes effective disease monitoring and prognosis. In this study, mutation profiles of the Calreticulin (CALR) gene and exons 12 and 14 within the Janus kinase 2 (JAK2 12 and 14) gene were investigated in Sudanese MPN patients. The subject were 140 Sudanese MPN patients; 70 patients were diagnosed with PV, 58 with ET, and 12 with PMF. Using TaqMan (R) Mutation Detection Assay followed by Sanger sequencing to confirm the results for JAK2 exons 14 (V617F) mutation and allele-specific PCR (AS-PCR) followed by Sanger sequencing for the four common mutations on exon 12 and CLAR mutation. CALR frameshift mutations were found in 8 (5.7%) patients with ET (i.e., 6 patients with type 1 mutation and 2 patients type 2) but not observed in PV or PMF patients. Mutation in JAK2 exon 14 were found in 70 (50.0%) patients (68.6% PV, 32.8% ET, and 50.0% PMF), while JAK2 exon 12 mutation were found in 6 (4.3%) PV patients. Patients with CALR mutations showed significant higher platelet levels compared to patients with JAK2 mutations (P=0.018). Patients with PV who exhibited JAK2 exon 12 mutations had significant high Hb levels and WBCs counts (P=0.002, P=0.001 respectively) but significant lower platelet counts (P=0.038) compared to wildtype. This study shows that the significance of CALR mutations appears to take issue among MPN subtypes.