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Early changes in gene expression profiles in AML patients during induction chemotherapy
Ingrid Jakobsen1,2, Max Sundkvist1, Niclas Björn1
1Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
BMC Genomics
|November 15, 2022
Summary
This study reveals that gene expression changes within the first two days of acute myeloid leukemia (AML) chemotherapy can predict treatment response. Early activation of NF-κB signaling and specific gene pathways in non-remission patients highlight potential biomarkers.
Area of Science:
- Genomics and Molecular Biology
- Hematology and Oncology
- Pharmacogenomics
Background:
- Understanding genetic factors influencing acute myeloid leukemia (AML) treatment response is crucial for personalized medicine.
- Emerging novel therapies necessitate better risk-adapted treatment strategies for AML patients.
- This pilot study investigates gene expression patterns during early induction chemotherapy in AML.
Purpose of the Study:
- To explore treatment-induced gene expression patterns in AML patients during the initial days of induction chemotherapy.
- To identify potential gene expression biomarkers associated with treatment response (complete remission vs. non-complete remission).
- To analyze differential gene expression (DGE) over time to understand chemotherapy's molecular effects.
Main Methods:
- Collected blood samples from ten AML patients at baseline, Day 1, and Day 2 of induction chemotherapy.
- Performed RNA sequencing to analyze differential gene expression (DGE) between time points.
- Utilized R package edgeR for DGE analysis and Ingenuity Pathway Analysis for pathway identification.
Main Results:
- Differential gene expression analysis revealed activation of NF-κB signaling pathways in 50% of patients by Day 2.
- Non-complete remission (nCR) patients showed activation of cell cycle, oncogenesis, and anti-apoptotic pathways, including STAT3.
- A significant induction of cytidine deaminase was observed in nCR patients, an enzyme linked to Ara-C deamination.
Conclusions:
- Time-course gene expression analysis is a feasible method to identify chemotherapy-affected pathways in AML.
- This approach can potentially uncover new drug targets and biomarkers for disease aggressiveness and treatment response.
- Larger cohort studies are required to fully elucidate the transcriptional basis of drug response in AML.
