TY - JOUR
T1 - An inflammatory state remodels the immune microenvironment and improves risk stratification in acute myeloid leukemia
AU - Lasry, Audrey
AU - Nadorp, Bettina
AU - Fornerod, Maarten
AU - Nicolet, Deedra
AU - Wu, Huiyun
AU - Walker, Christopher J.
AU - Sun, Zhengxi
AU - Witkowski, Matthew T.
AU - Tikhonova, Anastasia N.
AU - Guillamot-Ruano, Maria
AU - Cayanan, Geraldine
AU - Yeaton, Anna
AU - Robbins, Gabriel
AU - Obeng, Esther A.
AU - Tsirigos, Aristotelis
AU - Stone, Richard M.
AU - Byrd, John C.
AU - Pounds, Stanley
AU - Carroll, William L.
AU - Gruber, Tanja A.
AU - Eisfeld, Ann Kathrin
AU - Aifantis, Iannis
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85145196308&partnerID=8YFLogxK
U2 - 10.1038/s43018-022-00480-0
DO - 10.1038/s43018-022-00480-0
M3 - Article
C2 - 36581735
AN - SCOPUS:85145196308
SN - 2662-1347
VL - 4
SP - 27
EP - 42
JO - Nature Cancer
JF - Nature Cancer
IS - 1
ER -