1 Department of Clinical Biochemistry, Hematology Area, Faculty of Biochemical and Pharmaceutical Sciences, National University of Rosario, Rosario, Santa Fe, Argentina.
2 Institute of Experimental Physiology, Faculty of Biochemical and Pharmaceutical Sciences, CONICET - National University of Rosario, Rosario, Santa Fe, Argentina.
Research Article
World Journal of Advanced Research and Reviews, 2023, 19(03), 842-849
Article DOI: 10.30574/wjarr.2023.19.3.1840
Received on 04 August 2023; revised on 14 September 2023; accepted on 16 September 2023
Primary myelofibrosis (PMF), a BCR-ABL negative myeloproliferative neoplasm, is a heterogeneous clinical and genetic disorder with a poor prognosis. We aimed to study the mutational profile of driver genes (JAK2, CALR, and MPL) and high-molecular-risk (HMR) genes (ASXL1, EZH2, IDH1/2, and SRSF2) and their prognostic impact in 65 Argentine patients with PMF. Mutually exclusive driver mutations were identified in 88% of the cases and HMR mutations were detected in 37% of patients, including 37.5% of triple negative cases. ASXL1 and SRSF2 were the most frequently mutated HMR genes, and a significant association between these mutations was observed (P = 0.04). Additionally, age >65 years, lower hemoglobin level, constitutional symptoms, male sex, and bone marrow (BM) fibrosis grade ≥ 2 were correlated with ASXL1 mutations, and circulating blasts with SRSF2 mutations. HMR mutations were significantly associated with inferior overall survival (P < 0.001). These mutations were more frequent with increasing risk of DIPSS score and allowed us to identify patients with poor survival in intermediate DIPSS groups. The application of the MIPSS70 score stratified our patients into three risk groups, with significant differences in overall survival (P < 0.001). Interestingly, 85% of the patients who were upgraded to a higher risk category compared to the DIPSS score showed a HMR profile. In conclusion, our study contributes to the understanding of the mutational landscape in MFP, supports the integration of molecular data to improve prognostic models and reinforces the adverse prognostic impact of HMR mutations, particularly in ASXL1 and SRSF2 genes.
Mutations; Myeloproliferative neoplasm; Primary myelofibrosis; Prognostic impact
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Mara Jorgelina Ojeda, Georgina Maroni, Marina Misaña, María Victoria Schoepf, Daniela Bonavita and Arianna Flavia Pratti. Drivers and high-molecular-risk mutations in Argentine patients with primary myelofibrosis. World Journal of Advanced Research and Reviews, 2023, 19(3), 842-849. Article DOI: https://doi.org/10.30574/wjarr.2023.19.3.1840