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炎症状态重塑免疫微环境并改善急性髓系白血病的风险分层。

An inflammatory state remodels the immune microenvironment and improves risk stratification in acute myeloid leukemia.

机构信息

Department of Pathology, New York University School of Medicine, New York, NY, USA.

Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY, USA.

出版信息

Nat Cancer. 2023 Jan;4(1):27-42. doi: 10.1038/s43018-022-00480-0. Epub 2022 Dec 29.

DOI:10.1038/s43018-022-00480-0
PMID:36581735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9986885/
Abstract

Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor prognosis and limited treatment options. Here we provide a comprehensive census of the bone marrow immune microenvironment in adult and pediatric patients with AML. 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 patients with high-inflammation AML, as well as an increase in CD8GZMK 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 patients with AML. Addition of the iScore refines current risk stratifications for patients with AML and may enable identification of patients in need of more aggressive treatment. This work provides a framework for classifying patients with AML based on their immune microenvironment and a rationale for consideration of the inflammatory state in clinical settings.

摘要

急性髓系白血病（AML）是一种预后不良且治疗选择有限的血液系统恶性肿瘤。在这里，我们提供了成人和儿科 AML 患者骨髓免疫微环境的全面普查。我们在一组 AML 患者中描述了独特的炎症特征，这些特征与预后不良相关。我们发现了异常的 B 细胞，这是一种在高炎症 AML 患者中丰富的功能失调的 B 细胞亚型，以及 CD8GZMK 和调节性 T 细胞的增加，同时伴随着 T 细胞克隆扩增的减少。我们得出了一个与 AML 患者不良生存结果相关的炎症相关基因评分（iScore）。该评分的加入可以完善 AML 患者的现行风险分层，并可能有助于识别需要更积极治疗的患者。这项工作为基于免疫微环境对 AML 患者进行分类提供了一个框架，并为在临床环境中考虑炎症状态提供了一个理由。

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