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

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.

Automated summary

This study provides a comprehensive analysis of the bone marrow immune microenvironment in adult and pediatric AML patients. Unique inflammation signatures were identified in a subset of AML patients, which were associated with poor outcomes. Dysfunctional B-cell subtype, atypical B cells, were found to be enriched in high-inflammation AML patients, along with an increase in CD8(+)GZMK(+) and regulatory T cells, and a reduction in T-cell clonal expansion. An inflammation-associated gene score (iScore) was developed which predicts survival outcomes and refines current risk stratifications in AML patients. The study highlights the importance of considering the inflammatory state in clinical settings.