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Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up

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Cellular abundance-based prognostic model associated with deregulated gene expression of leukemic stem cells in acute

Dong-Jin Han^1,2,3, Sunmin Kim^1,2,3, Seo-Young Lee^1,2,3

¹Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Frontiers in Cell and Developmental Biology

|March 25, 2024

Summary

A new scoring system, the Leukemic Stem Cell Activity (LSCA) score, accurately predicts acute myeloid leukemia (AML) patient survival. This score uses deconvoluted cell-type abundance, offering a novel prognostic tool for AML.

Keywords:

acute myeloid leukemia cellular deconvolution leukemic stem cell prognostic model transcriptomic profiles

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Comprehensive Protocol to Sample and Process Bone Marrow for Measuring Measurable Residual Disease and Leukemic Stem Cells in Acute Myeloid Leukemia

Comprehensive Protocol to Sample and Process Bone Marrow for Measuring Measurable Residual Disease and Leukemic Stem Cells in Acute Myeloid Leukemia

Published on: March 5, 2018

Area of Science:

Hematology
Oncology
Bioinformatics

Background:

Leukemic stem cells (LSC) gene expression may influence patient survival in acute myeloid leukemia (AML).
Cellular deconvolution using gene expression data shows potential for AML prognosis but requires further validation.

Purpose of the Study:

To develop and validate a novel prognostic model for AML utilizing deconvoluted cellular abundances.
To assess the independent prognostic value of the new model in AML patients.

Main Methods:

A least absolute shrinkage and selection operator Cox regression model was developed using cell-type abundances from 422 AML samples.
The model was validated in two independent cohorts: TCGA-LAML (n=179) and Beat AML (n=451).
Prognostic performance was compared against existing models (LSC17, APS, CTC scores) using the area under the curve.

Main Results:

The Leukemic Stem Cell Activity (LSCA) score, incorporating 5 cell types, significantly differentiated survival in both validation cohorts.
LSCA score proved to be an independent prognostic factor, outperforming age, sex, and cytogenetic risk.
The LSCA score demonstrated comparable performance to established prognostic models.

Conclusions:

The LSCA score is a novel, validated prognostic tool for AML patients based solely on deconvoluted cell-type abundance.
This score correlates with LSC activity, offering insights into AML pathogenesis and prognosis.
The LSCA score provides a valuable addition to existing prognostic strategies in AML management.