TP53 Mutations in Myeloproliferative Neoplasms: Context-Dependent Evaluation of Prognostic Relevance

IF 10.1 1区 医学 Q1 HEMATOLOGY
Ayalew Tefferi, Maymona Abdelmagid, Giuseppe G. Loscocco, Saubia Fathima, Kebede H. Begna, Aref Al-Kali, James Foran, Jeanne Palmer, Talha Badar, Mrinal M. Patnaik, Kaaren K. Reichard, Rong He, Cinthya J. Zepeda Mendoza, Mithun Shah, Attilio Orazi, Daniel A. Arber, Animesh Pardanani, Alessandro M. Vannucchi, Devendra Hiwase, Naseema Gangat, Paola Guglielmelli
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引用次数: 0

Abstract

The clinical relevance of TP53 mutations (TP53 MUT ) in myeloproliferative neoplasms (MPN) and their prognostic interaction with MPN subtype designation has not been systematically studied. In the current study, 114 patients with MPN harboring TP53 MUT (VAF ≥ 2%) were evaluated for overall survival (OS), calculated from the time of TP53 MUT detection: chronic phase myelofibrosis (MF-CP; N = 61); blast-phase (MPN-BP; N = 31) or accelerated-phase (MPN-AP; N = 16) MPN, and polycythemia vera/essential thrombocythemia (PV/ET; N = 6). Sixty-five (57%) patients harbored International Consensus Classification (ICC)-defined multihit TP53 MUT and 56 (49%) monosomal/complex karyotype (MK/CK). Majority of MPN-BP (90%) and MPN-AP (81%) while 39% of MF-CP and none of PV/ET patients harbored multihit TP53 MUT . OS in MPN-BP and MPN-AP was equally dismal (median 6 vs. 4.5 months, respectively; p = 1.0), regardless of multihit configuration (p = 0.44), while OS in TP53 MUT MPN-BP/AP (N = 47; median 4 months) was inferior to that of a separate cohort (N = 49) with TP53 wild-type MPN-BP/AP (median 11 months; p < 0.01). OS in MF-CP was significantly shorter with multihit versus non-multihit TP53 MUT (median 10 vs. 35 months; HR 2.9; p < 0.01), independent of other MF-relevant genetic risk factors, including ASXL1/SRSF2/U2AF1 mutations. Multihit TP53 MUT was also associated with inferior survival following allogeneic stem cell transplant (ASCT): median 9 months versus “not reached” in patients with (N = 9) versus without (N = 8) multihit TP53 MUT (p < 0.01). The presence of multihit or non-multihit TP53 MUT in MPN-BP/AP or multihit TP53 MUT in MF-CP is associated with exceptionally poor prognosis and justifies inclusion into the ICC category of “myeloid neoplasms with mutated TP53.” By contrast, detection of non-multihit TP53 MUT, by itself, might not endanger short-term survival in MF-CP, PV, or ET.

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来源期刊
CiteScore
15.70
自引率
3.90%
发文量
363
审稿时长
3-6 weeks
期刊介绍: The American Journal of Hematology offers extensive coverage of experimental and clinical aspects of blood diseases in humans and animal models. The journal publishes original contributions in both non-malignant and malignant hematological diseases, encompassing clinical and basic studies in areas such as hemostasis, thrombosis, immunology, blood banking, and stem cell biology. Clinical translational reports highlighting innovative therapeutic approaches for the diagnosis and treatment of hematological diseases are actively encouraged.The American Journal of Hematology features regular original laboratory and clinical research articles, brief research reports, critical reviews, images in hematology, as well as letters and correspondence.
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