成人 AML 中涉及 11q23.3/KMT2A 的重排：突变景观和预后影响 - 一项 HARMONY 研究。
Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study.
发表日期：2024 Jul 04
作者：
Alberto Hernández-Sánchez, Teresa González, Marta Sobas, Eric Sträng, Gastone Castellani, María Abáigar, Peter J M Valk, Ángela Villaverde Ramiro, Axel Benner, Klaus H Metzeler, Raúl Azibeiro, Jesse M Tettero, Joaquín Martínez-López, Marta Pratcorona, Javier Martínez Elicegui, Ken I Mills, Christian Thiede, Guillermo Sanz, Konstanze Döhner, Michael Heuser, Torsten Haferlach, Amin T Turki, Dirk Reinhardt, Renate Schulze-Rath, Martje Barbus, Jesús María Hernández-Rivas, Brian Huntly, Gert Ossenkoppele, Hartmut Döhner, Lars Bullinger
来源：
Stem Cell Research & Therapy
摘要：
涉及 KMT2A 基因 (KMT2Ar) 的平衡重排是急性髓系白血病 (AML) 中反复出现的遗传异常，但对于不同融合伴侣的预后影响缺乏共识。此外，与 KMT2Ar 同时发生的基因突变对预后的影响尚未确定。从 HARMONY AML 数据库中选择了 205 名 KMT2Ar 成年患者，其中 185 名患者通过基于面板的下一代测序分析获得了突变信息。不同易位的总生存期 (OS) 相似，包括 t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756)。然而，强化治疗患者 OS 的独立预后因素是年龄 > 60 岁（HR 2.1，p = 0.001）、继发性 AML（HR 2.2，p = 0.043）、DNMT3A-mut（HR 2.1，p = 0.047）和 KRAS-突变（HR 2.0，p = 0.005）。在 60 岁以下的新发 AML 患者子集中，KRAS 和 TP53 是与预后最相关的突变基因，因为这两个基因中任何一个突变的患者的完全缓解率较低（50% vs 86%，p< 0.001）和较差的 OS（中位 7 个月与 30 个月，p< 0.001）。首次完全缓解时的同种异体造血干细胞移植能够改善 OS (p = 0.003)。我们的研究强调了成人 KMT2Ar AML 突变模式的重要性，并为这些患者的更准确的预后分层提供了新的见解。© 2024。作者。
Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients.© 2024. The Author(s).