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TP53 ‐Mutated Acute Myeloid Leukemia and Blast Phase Myeloproliferative Neoplasm: Distinct Mutation Leads to Poorer Prognosis
Author(s) -
Chen Dong,
Cantu Miguel,
Siddon Alexa,
Weinberg Olga K.
Publication year - 2025
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.14421
Subject(s) - myeloproliferative neoplasm , myeloid leukemia , mutation , cancer research , neoplasm , myeloproliferative disorders , myeloid , medicine , leukemia , biology , immunology , genetics , gene , myelofibrosis , pathology , bone marrow
ABSTRACT Patients with TP53 mutations in acute myeloid leukemia (AML) and blast phase myeloproliferative neoplasms (MPN‐BP) experience similar poor clinical outcomes. A retrospective analysis of 39 patients with TP53 mutations (23 with AML and 16 with MPN‐BP) revealed comparable mutation patterns associated with prognostic significance. A total of 47 distinct TP53 mutations were identified, including seven patients with multiple mutations. Based on clinical outcomes, we propose a two‐tiered risk stratification for TP53 ‐mutated AML and MPN‐BP. The high‐risk group mutations, such as splice site variants in Intron 4 (especially c.376), missense mutations in Exon 5 (notably p.R175H), and mutations in the oligomerization domain (OD), were associated with, particularly, worse overall survival (OS < 3 months). Conversely, single missense mutations in Exons 6 and 7 (notably p.Y220C, p.R248N, p.R248Q, and p.R248W), and mutations in the transactivation domain (TAD), constituted a low‐risk group and were associated with relatively better prognosis (median OS: 10.15 months for the low‐risk group vs. 1.3 months for the high‐risk group, p < 0.0001). These findings support the hypothesis that distinct TP53 mutations can lead to varying cellular effects, therapeutic responses, and clinical outcomes. Consequently, acute myeloid neoplasms (AML and MPN‐BP) harboring certain TP53 mutations may exhibit increased aggressiveness compared to other TP53 mutants, underscoring the need for prioritized clinical research and therapeutic targeting.