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Prognostic impact of TP53 mutations in patients with MPN
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The prognostic impact of TP53 mutations is well characterized in AML and MDS, and the ICC 2022 guidelines include a new disease category of “myeloid neoplasms with mutated TP53”.1 However, the prognostic relevance of TP53 mutations in MPN and their interaction with MPN subtypes has not been systematically studied. A retrospective analysis by Tefferi et al.1 assessed the prognostic relevance of TP53 mutations in 144 adult patients with TP53-mutated MPN (PV, n = 3; ET, n = 3; MF-CP, n = 61; MPN-AP, n = 16; MPN-BP, n = 31). Diagnostic criteria and TP53 allelic state were assessed according to the ICC 2022 guidelines and patients were evaluated for OS, calculated from the time of TP53 mutation detection. The impact of TP53 mutation and allelic state on survival after ASCT were also assessed. Results were published in the American Journal of Hematology.1 |
| Key learnings |
| OS in MPN-BP and MPN-AP were very poor (median, 6 months and 4.5 months, respectively; p = 1.0), regardless of multi-hit configuration (p = 0.44). OS in TP53-mutated MPN-BP/AP (n = 47; median, 4 months) was inferior to TP53 wild-type MPN-BP/AP (n = 49*; median, 11 months; p < 0.01). |
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Multi-hit TP53 mutations were associated with significantly reduced median OS vs non-multi-hit TP53 mutations in patients with MF-CP (10 months vs 35 months; p < 0.01) independent of other MF genetic risk factors, including ASXL1/SRSF2/U2AF1 mutations. |
| Multi-hit TP53 mutations were also associated with inferior survival following ASCT, with a median OS of 9 months in patients with multi-hit mutations (n = 9) vs not reached in those without (n = 8) (p < 0.01). |
| The presence of TP53 mutations in MPN-BP/AP or multi-hit TP53 mutations in MF-CP is associated with very poor prognosis, supporting their classification within the “myeloid neoplasms with mutated TP53” ICC category. Conversely, non-multi-hit TP53 mutations may not impact short-term survival in patients with MF-CP, PV, or ET. |
*Separate Mayo Clinic cohort.
Abbreviations: AML, acute myeloid leukemia; ASCT; allogeneic stem cell transplant; CI, confidence interval; ET, essential thrombocytosis; HR, hazard ratio; ICC, International Consensus Classification; MDS, myelodysplastic syndromes; MF, myelofibrosis MF-CP, chronic phase MF; MPN, myeloproliferative neoplasms; MPN-AP, accelerated-phase MPN; MPN-BP, blast-phase MPN; OS, overall survival; PV, polycythemia vera.
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