Audrey Lasry, B. Nadorp, M. Fornerod, D. Nicolet, Huiyun Wu, C. Walker, Zhengxi Sun, Matthew T. Witkowski, Anastasia N. Tikhonova, Maria Guillamot, Geraldine Cayanan, Anna H. Yeaton, T. Gruber, Ann-Kathrin Eisfeld, I. Aifantis
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引用次数: 0
摘要
急性髓性白血病(AML)是一种预后不良且治疗方案有限的造血恶性肿瘤。在这里,我们提供了成人和儿童AML患者骨髓免疫微环境的全面单细胞rna测序普查。我们在AML患者的一个亚群中描述了独特的炎症特征,与不良预后相关。我们鉴定了非典型B细胞,一种在高炎症性AML患者中富集的功能失调B细胞亚型,以及CD8+ GZMK+和调节性T细胞的增加,伴随着T细胞克隆扩增的减少。我们得出了与AML患者不良生存结果相关的炎症相关基因评分(iScore)。iScore的加入细化了AML患者目前的风险分层,并可能使识别需要更积极治疗的患者成为可能。这项工作提供了基于免疫微环境对AML患者进行分类的第一个框架,并为临床环境中考虑炎症状态提供了依据。引文格式:Audrey Lasry, Bettina Nadorp, Maarten Fornerod, Deedra Nicolet,吴慧云,Christopher J Walker,孙正曦,Matthew T Witkowski, Anastasia N Tikhonova, Maria Guillamot, Geraldine Cayanan, Anna Yeaton, Tanja A Gruber, Ann-Kathrin Eisfeld, Iannis Aifantis。炎症重塑急性髓性白血病的免疫微环境[摘要]。摘自:AACR特别会议论文集:急性髓性白血病和骨髓增生异常综合征;2023年1月23-25日;费城(PA): AACR;血癌杂志[j]; 2009;4(3 -增刊):摘要/ Abstract
Abstract A20: Inflammation remodels the immune microenvironment in acute myeloid leukemia
Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor prognosis and limited treatment options. Here we provide a comprehensive single cell RNA-Sequencing census of the bone marrow immune microenvironment in adult and pediatric AML patients. We characterize unique inflammation signatures in a subset of AML patients, associated with inferior outcomes. We identify atypical B cells, a dysfunctional B cell subtype enriched in high-inflammation AML patients, as well as an increase in CD8+ GZMK+ and regulatory T cells, accompanied by a reduction in T cell clonal expansion. We derive an inflammation-associated gene score (iScore) that associates with poor survival outcomes in AML patients. Addition of the iScore refines current risk stratifications for AML patients and may enable identification of patients in need of more aggressive treatment. This work provides a first framework for classifying AML patients based on their immune microenvironment and a rationale for consideration of the inflammatory state in clinical settings.
Citation Format: Audrey Lasry, Bettina Nadorp, Maarten Fornerod, Deedra Nicolet, Huiyun Wu, Christopher J Walker, Zhengxi Sun, Matthew T Witkowski, Anastasia N Tikhonova, Maria Guillamot, Geraldine Cayanan, Anna Yeaton, Tanja A Gruber, Ann-Kathrin Eisfeld, Iannis Aifantis. Inflammation remodels the immune microenvironment in acute myeloid leukemia [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr A20.
期刊介绍:
The journal Blood Cancer Discovery publishes high-quality Research Articles and Briefs that focus on major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The topics covered include molecular and cellular features of pathogenesis, therapy response and relapse, transcriptional circuits, stem cells, differentiation, microenvironment, metabolism, immunity, mutagenesis, and clonal evolution. These subjects are investigated in both animal disease models and high-dimensional clinical data landscapes.
The journal also welcomes submissions on new pharmacological, biological, and living cell therapies, as well as new diagnostic tools. They are interested in prognostic, diagnostic, and pharmacodynamic biomarkers, and computational and machine learning approaches to personalized medicine. The scope of submissions ranges from preclinical proof of concept to clinical trials and real-world evidence.
Blood Cancer Discovery serves as a forum for diverse ideas that shape future research directions in hematooncology. In addition to Research Articles and Briefs, the journal also publishes Reviews, Perspectives, and Commentaries on topics of broad interest in the field.