Back to Search
Start Over
Molecular profiling of pre- and post- 5-azacytidine myelodysplastic syndrome samples identifies predictors of response
- Source :
- Frontiers in Oncology, Vol 14 (2024)
- Publication Year :
- 2024
- Publisher :
- Frontiers Media S.A., 2024.
-
Abstract
- Treatment with the hypomethylating agent 5-azacytidine (AZA) increases survival in high-risk (HR) myelodysplastic syndrome (MDS) patients, but predicting patient response and overall survival remains challenging. To address these issues, we analyzed mutational and transcriptional profiles in CD34+ hematopoietic stem/progenitor cells (HSPCs) before and following AZA therapy in MDS patients. AZA treatment led to a greater reduction in the mutational burden in both blast and hematological responders than non-responders. Blast and hematological responders showed transcriptional evidence of pre-treatment enrichment for pathways such as oxidative phosphorylation, MYC targets, and mTORC1 signaling. While blast non-response was associated with TNFa signaling and leukemia stem cell signature, hematological non-response was associated with cell-cycle related pathways. AZA induced similar transcriptional responses in MDS patients regardless of response type. Comparison of blast responders and non-responders to normal controls, allowed us to generate a transcriptional classifier that could predict AZA response and survival. This classifier outperformed a previously developed gene signature in a second MDS patient cohort, but signatures of hematological responses were unable to predict survival. Overall, these studies characterize the molecular consequences of AZA treatment in MDS HSPCs and identify a potential tool for predicting AZA therapy responses and overall survival prior to initiation of therapy.
Details
- Language :
- English
- ISSN :
- 2234943X
- Volume :
- 14
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Oncology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7fb6c7685b74917942b55da558c1fcc
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fonc.2024.1438052