Language

English

Publication Date

11-1-2024

Journal

Life Science Alliance

DOI

10.26508/lsa.202402674

PMID

39191488

PMCID

PMC11358707

PubMedCentral® Posted Date

8-27-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Pediatric acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis and high relapse rate. Current challenges in the identification of immunotherapy targets arise from patient-specific blast immunophenotypes and their change during disease progression. To overcome this, we present a new computational research tool to rapidly identify malignant cells. We generated single-cell flow cytometry profiles of 21 pediatric AML patients with matched samples at diagnosis, remission, and relapse. We coupled a classifier to an autoencoder for anomaly detection and classified malignant blasts with 90% accuracy. Moreover, our method assigns a developmental stage to blasts at the single-cell level, improving current classification approaches based on differentiation of the dominant phenotype. We observed major immunophenotype and developmental stage alterations between diagnosis and relapse. Patients with KMT2A rearrangement had more profound changes in their blast immunophenotypes at relapse compared to patients with other molecular features. Our method provides new insights into the immunophenotypic composition of AML blasts in an unbiased fashion and can help to define immunotherapy targets that might improve personalized AML treatment.

Keywords

Humans, Leukemia, Myeloid, Acute, Child, Single-Cell Analysis, Immunophenotyping, Female, Male, Child, Preschool, Adolescent, Myeloid-Lymphoid Leukemia Protein, Flow Cytometry, Infant, Histone-Lysine N-Methyltransferase, Computational Biology, Prognosis

Published Open-Access

yes

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.