Mitochondrial gene expression signature predicts prognosis of pediatric acute myeloid leukemia patients
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Updated: Aug 2, 2026
Assessment of the Metabolic Profile of Primary Leukemia Cells
Published on: November 21, 2018
Shilpi Chaudhary1, Shuvadeep Ganguly1, Jayanth Kumar Palanichamy2
1Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.
Insights
Researchers identified key mitochondria-related genes in pediatric acute myeloid leukemia (AML). A novel 3-gene signature accurately predicts patient survival, offering new prognostic insights for childhood AML.
Area of Science:
- Mitochondrial biology
- Pediatric oncology
- Molecular diagnostics
Background:
- Mitochondria-related gene expression is poorly understood in pediatric acute myeloid leukemia (AML).
- Identifying these genes is crucial for understanding AML pathogenesis and developing prognostic tools.
Purpose of the Study:
- To identify mitochondria-related differentially expressed genes (DEGs) in pediatric AML.
- To assess the prognostic significance of these DEGs.
- To develop and validate a gene signature for predicting survival in pediatric AML.
Main Methods:
- Transcriptomic profiling of pediatric AML samples.
- Identification and validation of DEGs using real-time PCR.
- Development of a prognostic risk score based on validated DEGs.
- External validation of the risk score using The Cancer Genome Atlas (TCGA) AML dataset.
Main Results:
- Sixteen out of twenty selected mitochondria-related DEGs were significantly dysregulated.
- Upregulation of SDHC, CLIC1 and downregulation of SLC25A29 independently predicted inferior overall survival (OS).
- A 3-gene risk score was independently predictive of survival, outperforming ELN risk categorization and validated in an external cohort.
Conclusions:
- Mitochondria-related DEGs hold significant prognostic value in pediatric AML.
- A novel, externally validated 3-gene signature effectively predicts survival in pediatric AML patients.
- This gene signature can aid in risk stratification and personalized treatment strategies for childhood AML.
Introduction:
Gene expression profile of mitochondrial-related genes is not well deciphered in pediatric acute myeloid leukaemia (AML). We aimed to identify mitochondria-related differentially expressed genes (DEGs) in pediatric AML with their prognostic significance.
Methods:
Children with de novo AML were included prospectively between July 2016-December 2019. Transcriptomic profiling was done for a subset of samples, stratified by mtDNA copy number. Top mitochondria-related DEGs were identified and validated by real-time PCR. A prognostic gene signature risk score was formulated using DEGs independently predictive of overall survival (OS) in multivariable analysis. Predictive ability of the risk score was estimated along with external validation in The Tumor Genome Atlas (TCGA) AML dataset.
Results:
In 143 children with AML, twenty mitochondria-related DEGs were selected for validation, of which 16 were found to be significantly dysregulated. Upregulation of SDHC (p<0.001), CLIC1 (p=0.013) and downregulation of SLC25A29 (p<0.001) were independently predictive of inferior OS, and included for developing prognostic risk score. The risk score model was independently predictive of survival over and above ELN risk categorization (Harrell's c-index: 0.675). High-risk patients (risk score above median) had significantly inferior OS (p<0.001) and event free survival (p<0.001); they were associated with poor-risk cytogenetics (p=0.021), ELN intermediate/poor risk group (p=0.016), absence of RUNX1-RUNX1T1 (p=0.027), and not attaining remission (p=0.016). On external validation, the risk score also predicted OS (p=0.019) in TCGA dataset.
Discussion:
We identified and validated mitochondria-related DEGs with prognostic impact in pediatric AML and also developed a novel 3-gene based externally validated gene signature predictive of survival.
