A Three-Gene Interferon Signature Predicts Sustained Complete Remission in Pediatric AML Patients

Area of Science:

• Immunology
• Oncology
• Genetics

Background:

• The bone marrow microenvironment's role in solid tumors is established, but its significance in acute leukemias, particularly pediatric acute myeloid leukemia (AML), is underexplored.
• Understanding the immune landscape of AML is crucial for improving diagnosis, prognosis, and therapeutic strategies.

Purpose of the Study:

• To investigate the predictive value of the acute myeloid leukemia (AML) bone marrow microenvironment for chemosensitivity and long-term remission in pediatric patients.
• To identify biomarkers within the leukemia microenvironment that can refine risk stratification for standard-risk pediatric AML patients.

Main Methods:

• Analysis of 32 non-promyelocytic pediatric AML patients at diagnosis using NanoString PanCancer IO 360 assay, RNA sequencing, and deep-phenotype flow cytometry.
• Validation of findings using the pediatric TARGET AML dataset.

Main Results:

• A three-gene interferon (IFN)-related signature (GBP1, PARP12, TRAT1) identified patients with chemosensitive disease and reduced minimal residual disease.
• This signature stratified patients, with high gene expression at diagnosis correlating with longer overall survival, especially within the standard-risk group.
• The favorable prognosis microenvironment showed enrichment of non-exhausted CD4+ and CD8+ T cells and expanded CD8+ T effector memory cells (TEMRA).

Conclusions:

• The bone marrow microenvironment plays a critical role in pediatric AML outcomes.
• The identified gene signature offers a tool for refined risk stratification of standard-risk pediatric AML patients.
• These findings provide a basis for developing immune-targeted therapies for pediatric AML.