# Transcriptomic Diversity of Pediatric Acute Myeloid Leukemia Genetic Drivers Correlates With Clinical Outcome and Expression of Stemness‐Related Genes

## TL;DR

This study finds that higher transcriptomic diversity in pediatric acute myeloid leukemia is linked to worse survival and stemness-related gene expression.

## Contribution

The paper introduces transcriptomic diversity as a novel prognostic indicator in pediatric AML.

## Key findings

- High diversity oncogenic drivers correlate with poorer overall survival in pediatric AML patients.
- Stemness-related genes are enriched in patients with high transcriptomic diversity.
- High diversity oncogenic drivers show worse survival even with similar transcriptomic profiles.

## Abstract

Pediatric acute myeloid leukemia (pAML) is comprised of a diverse set of oncogenic drivers (ODs) that have been risk‐stratified to inform prognosis and therapeutic decision‐making. Despite proteomic, transcriptomic, genetic, and epigenetic characterization of the pAML landscape, questions still remain about why certain ODs have poorer prognoses than others.

We analyze a large pAML bulk‐RNA dataset (n = 435) and organize ODs along an axis of transcriptomic diversity by calculating the Simpson Diversity Index (SDI) of individual ODs.

When comparing patients with low diversity ODs to patients with high diversity ODs, we observe poorer overall survival (HR = 1.877, 95% CI: 1.377–2.558, p = 0.0002) among patients harboring high diversity ODs in addition to an enrichment of stemness‐related genes. We observe poorer survival of patients with high diversity ODs even when comparing patients with similar transcriptomic profiles (HR = 3.443, 95% CI: 1.817–6.525, p = 0.0028).

We identify a link between transcriptomic diversity, expression of stemness‐related genes, and clinical outcome. Higher transcriptomic heterogeneity exhibited by high diversity ODs warrants further attention when identifying patients who can benefit from novel or high‐intensity therapy.