Imbalanced receptors, gene signatures, and function of NK subsets predicts poor clinical outcomes in AML

Abstract NK cells mediate anti-leukemic immunosurveillance in AML. We hypothesized that impaired predict poor outcomes analyzed the expression of receptors on CD56 cell subsets and their corresponding ligands CD45dim blast by flow cytometry 100 AML 17 healthy bone marrows. Risk stratification, complete remission, relapse, measurable residual disease, overall survival, relapse-free ligand expression, function, degranulation were evaluated. Additionally, we mapped transcriptional landscape AML-NK using single-cell RNA-seq. The activating CD56dim was decreased adverse risk, MRD+ patients. Inhibitory increased MRD+. patients with higher receptor while inhibitory increased. Patients a lower frequency showed less killing rates. Transcriptionally, observed an enrichment inflammatory-associated pathways upregulation AML, especially worst prognosis. Our data indicate exhaustion, high receptors, leads to cytotoxicity can Also, selective pressure together imbalanced may vary both leukemic cells. Closing these gaps knowledge NK-mediated immune evasion leukemia is significant interest for targeting microenvironment cell-mediated immunotherapy. "division funds" - 3117175