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• W2300536723 abstract "Background: The median survival of patients with primary myelofibrosis (PMF) is 5 to 7 years after diagnosis. In the majority of patients with PMF somatic mutations were detected either in Janus Kinase 2 (JAK2; in 60% of patients), Calreticulin (CALR; in 25% of patients) or MPL (in 5% of patients) genes. Neither mutation was detected 5% to 10% of PMF patients. Patients with mutated JAK2 are known to have a more aggressive disease compared to patients with mutated CALR. However patients with mutated JAK2 and high allele burden have a favorable outcome compared to patients with a low mutated JAK2 burden. Aim: To develop a model that uses genetic information to predict survival outcome of patients with PMF. Patients and Methods: Bone marrow samples were collected from 344 patients with PMF that were followed at MD Anderson Cancer Center between 2000 and 2013 (157 months). All samples were screened for JAK2 and for mutations in CALR. Patients who did not have a mutation in either gene were also screened for mutations in MPL. Results: In 226 patients (66%) JAK2 was detected and in 43 (13%) CALR was mutated. Of the 75 patients who did not have JAK2 or CALR mutations, 16 (21%) had mutated MPL. In 59 patients (17%), none of those mutations was detected. In the 226 patients who harbored the JAK2 mutation, a cut-point of 50% dichotomized patients into those with a high JAK2 burden and a favorable overall survival (OS; median OS: 80 months) and those with a low JAK2 burden and an adverse OS (median OS: 50 months). Age (above 65 years) and mutation status (low JAK2 burden or triple-negative) were independent risk factors. Patients with a favorable mutation status and age below 65 had a median survival of 126 months (n 1⁄4 82). Patients with either one risk factor, age above 65 (n 1⁄4 88) or adverse mutation status (n 1⁄4 87) had intermediate survival expectancy. The two risk factors were additive and patients age > 65 years and adverse mutation status (n 1⁄4 87) had a median survival of 35 months. Conclusions: Age and mutation status are independent predictors of survival in patients with PMF and stratify patients into 4 groups of equal size with very different survival outcome. 703 Mutational Profiling of JAK2V617F vs. CALR mutated Primary Myelofibrosis Fabio Santos, Renato Puga, Bianca Lisboa, Welbert Pereira, Mariana Miyagi, Evelyn Mata, Tarcila Datoguia, Isabel Bello, Michelli Diniz, Sandra Nakashima, Guilherme Perini, Ricardo Helman, Nelson Hamerschlak, Paulo Campregher Hematology/Oncology, Hospital Israelita Albert Einstein" @default.
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• W2300536723 date "2015-06-01" @default.
• W2300536723 modified "2023-09-27" @default.
• W2300536723 title "Prognostic model based on JAK2, CALR and MPL mutation status and age predicts the survival outcome of patients with primary myelofibrosis" @default.
• W2300536723 doi "https://doi.org/10.1016/j.clml.2015.04.125" @default.
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