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Genomic profiling for decision-making in post‑PV and post‑ET secondary MF
Results from a study using the Myelofibrosis Secondary to PV and ET (MYSEC) project database, evaluating the prognostic significance of genomic and cytogenetic profiling in 644 patients with post-polycythemia vera (PV; n = 314) or post-essential thrombocythemia (ET; n = 330) secondary myelofibrosis (sMF), were published in Blood by Mora et al. The primary objective of this study was to develop a prognostic model (PM) that considers cancer gene variants (CGVs) and karyotype for sMF.
Key data: Overall, 66.6% of study participants harbored at least one CGV, with ASXL1 (29.7%), TET2 (19.9%), DNMT3A (6.7%), and EZH2 (5.1%) being the most frequently involved. There was a greater prevalence of CGVs in post‑ET vs post‑PV sMF (p = 0.01). Patients with ASXL1 (8.2 vs 11.2 years; p = 0.004), U2AF1 (3.9 vs 10.1 years; p < 0.001), TP53 (2.5 vs 9.7 years; p < 0.001), and SRSF2 (2.1 vs 10.1 years; p < 0.001) CGVs had a reduced median overall survival (OS) vs those who did not. U2AF1, TP53, or SRSF2 variants (UTS) conferred a lower median OS vs ASXL1 without UTS (4.1 vs 8.4 years; p < 0.001). Based on this, the mutation-enhanced MYSEC-molecular PM (MYSEC-mPM) stratified patients into four risk groups with different median OS: low (18.0 years), intermediate‑1 (8.8 years), intermediate‑2 (4.6 years), and high risk (1.9 years; p < 0.001).
Key learning: Results suggest that MYSEC-PM tools, enhanced by genomic profiling, may improve survival prediction in sMF, enabling informed treatment decision-making.
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