Transcriptomic analysis reveals proinflammatory signatures associated with acute myeloid leukemia progression

Area of Science:

• Hematology
• Genomics
• Molecular Biology

Background:

• Genomic and transcriptomic alterations drive acute myeloid leukemia (AML) initiation and progression.
• Improved risk classification and treatment strategies have emerged from extensive AML research.
• Detailed molecular profiling of longitudinal AML samples is limited, hindering efforts to address relapse and therapy resistance.

Purpose of the Study:

• To perform transcriptome-wide RNA sequencing on longitudinal AML samples (diagnosis, relapse, primary resistant).
• To identify gene expression patterns associated with event-free survival, relapse, and resistance in adult and pediatric AML.
• To uncover novel molecular targets for personalized AML therapies.

Main Methods:

• Transcriptome-wide RNA sequencing of 47 adult and 23 pediatric AML patient samples.
• Analysis of gene expression in longitudinal samples (diagnosis, relapse, primary resistant).
• Application of machine learning and network-based analyses to identify predictive gene signatures.

Main Results:

• Overexpression of GLI2 and IL1R1, and downregulation of ST18 associated with shorter event-free survival.
• CR1 downregulation and DPEP1 upregulation linked to AML relapse in both adult and pediatric cohorts.
• CD6 overexpression and INSR downregulation identified as key predictive genes for adult AML relapse.

Conclusions:

• Gene expression changes, including those related to inflammation, are critical in AML progression and relapse.
• Identified differentially expressed genes (e.g., GLI2, IL1R1, ST18, CR1, DPEP1, CD6, INSR) provide a foundation for novel therapeutic strategies.
• Findings support the development of personalized drug targets to improve AML cure rates and treatment efficacy.