TOPLINE:

Acute myeloid leukemia (AML) impairs neutrophil maturation in bone marrow, with mature neutrophils decreasing by over 78% in marrow and 89% in blood. AML-exposed neutrophils acquire inflammatory characteristics and suppress T-cell function, contributing to increased infection risk.

METHODOLOGY:

• Researchers utilized a neutrophil reporter Ly6G-tdTomato mouse model where primary leukemic cells were transplanted into nonirradiated neutrophil reporter hosts.
• Analysis included flow cytometry and transcriptomics of AML-exposed neutrophils, with single-cell RNA sequencing performed on bone marrow-derived viable Ly6G+ neutrophils.
• Investigators examined fresh marrow and blood samples from newly diagnosed patients with AML (n > 10) to evaluate neutrophils using a human neutrophil-specific flow panel.
• A cytokine screen was conducted on marrow neutrophils to identify factors affecting biology, with nuclear factor κB signaling driving CD14 expression.

TAKEAWAY:

• AML-exposed neutrophils exhibited significant maturation impairment, with mature neutrophils decreasing by 78.67% ± 2.05% in bone marrow and 89.08% ± 3.55% in blood compared with control individuals (SD, 2.05-3.55).
• CD14 surface expression increased to 60.1% ± 11.5% of mature neutrophils in blood during AML compared with 3.2% ± 2.6% in control individuals, with a correlation coefficient, 0.51 between CD14+ neutrophils and white blood cell counts.
• Transcriptomic analysis revealed AML-exposed neutrophils had higher inflammation signatures and decreased maturation scores compared with their healthy counterparts.
• AML-exposed CD14+ neutrophils demonstrated immunosuppressive properties by inhibiting T-cell proliferation by 58.9% compared with their healthy counterparts.

IN PRACTICE:

“Collectively, these data show that AML-associated inflammation alters neutrophil granulopoiesis, impairs neutrophil function, and drives immunosuppression, thereby contributing to patient susceptibility to infection,” the authors of the study wrote.

SOURCE:

This study was led by Paran Goel, Division of Hematology and Oncology, Department of Medicine, O’Neal Comprehensive Cancer Center at The University of Alabama at Birmingham. It was published online on October 2 in Blood.

LIMITATIONS:

According to the authors, conventional methods often rely on Ficoll-isolated peripheral blood mononuclear cells, which may not capture neutrophil complexities in AML. Additionally, surface markers to identify neutrophil subpopulations are challenging to interpret, especially during inflammatory conditions.

DISCLOSURES:

This study received funding from multiple sources including the National Heart, Lung, and Blood Institute; National Institutes of Health; the Mark Foundation Endeavor Award; and various training program grants. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.