Cellular hierarchy for understanding heterogeneity of acute myeloid leukaemia with t(8;21)/RUNX1-RUNX1T1

IF 4.6 2区 医学 Q2 IMMUNOLOGY
Yibo Wu, Xiaolin Yuan, Xiaoyu Lai, Lizhen Liu, Yue Liang, Lihong Ni, Luxin Yang, Shanshan Hu, Jimin Shi, Jian Yu, Yanmin Zhao, Weiyan Zheng, Jie Sun, Yuanyuan Zhu, Wenjun Wu, Zhen Cai, He Huang, Shanshan Pei, Yi Luo
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引用次数: 0

Abstract

Objectives

Differentiation hierarchies in myeloid malignancies influence therapeutic response and prognosis. Acute myeloid leukaemia (AML) with t(8;21) is one of the most recurrent genetic subtypes of AML and is considered a distinct entity with shared characteristics. However, clinical outcomes remain markedly heterogeneous. This study aimed to investigate the relationship between leukaemic arrest at specific differentiation stages, genomic profiles and clinical outcomes in t(8;21) AML.

Methods

We conducted a retrospective study involving 338 patients with t(8;21) AML from three clinical centres in China. Patients received either chemotherapy alone (49.11%, n = 166) or chemotherapy followed by allogeneic haematopoietic stem cell transplantation (allo-HSCT; 41.72%, n = 141). Immunophenotypic profiling classified patients into progenitor subgroups: MPP (20.12%, n = 68), lymphoid-primed multi-potent progenitor (14.50%, n = 49), CMP (12.72%, n = 43), GMP (24.85%, n = 84) and GP/MP (10.36%, n = 35). Based on differentiation stage, patients were categorised as primitive (Immuno-Prim; 47.34%, n = 160) or monocytic (Immuno-Mono; 35.21%, n = 119).

Results

The Immuno-Mono group was associated with lower 2-year overall survival (OS) and a higher 2-year cumulative incidence of relapse (CIR) compared to the Immuno-Prim group. Patients with a KIT mutation had poorer 2-year OS and higher 2-year CIR than those without the mutation. In the allo-HSCT cohort, the Immuno-Mono group continued to show lower 2-year OS and higher 2-year CIR relative to the Immuno-Prim group. Neither gene mutations (aside from KIT) nor chromosomal losses significantly affected OS or CIR.

Conclusions

Leukaemic differentiation stage independently predicts post-treatment outcomes in t(8;21) AML. Arrest at specific myeloid stages correlates significantly with genetic aberrations, clinical presentation, therapeutic response and survival.

Abstract Image

细胞层级对t(8;21)/RUNX1-RUNX1T1急性髓系白血病异质性的认识
目的髓系恶性肿瘤的分化等级影响治疗效果和预后。急性髓性白血病(AML)伴t(8;21)是AML最常复发的遗传亚型之一,被认为是具有共同特征的独特实体。然而,临床结果仍然存在明显的异质性。本研究旨在探讨t(8;21) AML在特定分化阶段白血病骤停、基因组谱和临床结局之间的关系。方法我们对来自中国三个临床中心的338例t(8;21) AML患者进行了回顾性研究。患者接受单独化疗(49.11%,n = 166)或化疗后异体造血干细胞移植(alloo - hsct;41.72%, n = 141)。免疫表型分析将患者分为祖细胞亚组:MPP (20.12%, n = 68)、淋巴细胞引发的多能祖细胞(14.50%,n = 49)、CMP (12.72%, n = 43)、GMP (24.85%, n = 84)和GP/MP (10.36%, n = 35)。根据分化阶段,将患者分为原始(immune - prim);47.34%, n = 160)或单核细胞(immune - mono;35.21%, n = 119)。结果与免疫- prim组相比,免疫- mono组的2年总生存期(OS)较低,2年累积复发发生率(CIR)较高。与没有突变的患者相比,KIT突变患者的2年OS较差,2年CIR较高。在同种hsct队列中,相对于免疫- prim组,免疫- mono组继续显示较低的2年OS和较高的2年CIR。基因突变(KIT除外)和染色体缺失均未显著影响OS或CIR。结论白血病分化阶段独立预测t(8;21) AML治疗后预后。在特定的髓细胞阶段的阻滞与基因畸变、临床表现、治疗反应和生存显著相关。
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来源期刊
Clinical & Translational Immunology
Clinical & Translational Immunology Medicine-Immunology and Allergy
CiteScore
12.00
自引率
1.70%
发文量
77
审稿时长
13 weeks
期刊介绍: Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.
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