A proteogenomic gene signature defines prognostic subgroups highlighting PI3K/AKT/mTOR signaling pathway as a therapeutic vulnerability in myeloid malignancies.

ABSTRACT:

Introduction

Myeloid malignancies, including acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN), exhibit overlapping pathophysiology. Chronic MPNs can transform into secondary AML (sAML), which is associated with poor prognosis and limited treatment options. However, the process and prognostic significance of leukemic transformation remain incompletely understood.

Method

Through a two-sample bidirectional Mendelian randomization (MR) analysis, we showed that genetic liability to MPN significantly predicts the risk of developing AML, establishing MPN as the precursor to leukemia. To identify mediators of this risk, we integrated population-level plasma proteomics data, identifying 55 proteins associated with MPN. Upon integrative analysis with the BEAT-AML co

SUBMITTER: He F 

PROVIDER: S-EPMC12853910 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature