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CALR and ASXL1 mutations-based molecular prognostication in primary myelofibrosis: an international study of 570 patients

2014; Springer Nature; Volume: 28; Issue: 7 Linguagem: Inglês

10.1038/leu.2014.57

1476-5551

Ayalew Tefferi, Paola Guglielmelli, Terra L. Lasho, Giada Rotunno, Christy Finke, C Mannarelli, Alem A. Belachew, Alessandro Pancrazzi, Emnet A Wassie, Rhett P. Ketterling, Curtis A. Hanson, Animesh Pardanani, Alessandro M. Vannucchi,

Chronic Myeloid Leukemia Treatments

Current prognostication in primary myelofibrosis (PMF) is based on the dynamic international prognostic scoring system (DIPSS)-plus, which employs clinical and cytogenetic variables. We recently reported DIPSS-plus independent prognostic significance for calreticulin (CALR) (favorable) and ASXL1 (unfavorable) mutations. In the current study, 570 PMF patients were recruited for derivation (n=277) and validation (n=293) of a molecular prognostic model based on these two mutations. Survival was the longest in CALR(+)ASXL1(-) (median 10.4 years) and shortest in CALR(-)ASXL1(+) patients (median, 2.3 years; hazard ratio (HR), 5.9; 95% confidence interval (CI), 3.5-10.0). CALR(+)ASXL1(+) and CALR(-)ASXL1(-) patients had similar survival and were grouped together in an intermediate-risk category (median survival, 5.8 years; HR, 2.5; 95% CI, 1.5-4.0). The CALR/ASXL1 mutations-based prognostic model was DIPSS-plus independent (P 65 years vs 2.7 for unfavorable karyotype. These observations signify immediate clinical relevance and warrant i) CALR and ASXL1 mutation determination in all patients with PMF and ii) molecular revision of DIPSS-plus.