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

炎症状态可重塑免疫微环境,并改善急性髓系白血病的风险分层。

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作者:Audrey Lasry # ,Bettina Nadorp # ,Maarten Fornerod ,Deedra Nicolet ,Huiyun Wu ,Christopher J Walker ,Zhengxi Sun ,Matthew T Witkowski ,Anastasia N Tikhonova ,Maria Guillamot-Ruano ,Geraldine Cayanan ,Anna Yeaton ,Gabriel Robbins ,Esther A Obeng ,Aristotelis Tsirigos ,Richard M Stone ,John C Byrd ,Stanley Pounds ,William L Carroll ,Tanja A Gruber ,Ann-Kathrin Eisfeld ,Iannis Aifantis

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 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 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.

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