Detection of Fusion Genes Using RNA Sequencing in Acute Leukemia

Area of Science:

• Hematology
• Molecular Diagnostics
• Genomics

Background:

• Fusion genes are critical drivers in acute leukemia development.
• Current diagnostic methods struggle to detect the full spectrum of fusion genes in updated classifications.
• Accurate fusion gene identification is essential for precise acute leukemia diagnosis and treatment.

Purpose of the Study:

• To evaluate the diagnostic performance of whole RNA sequencing (RNA-seq) for fusion gene detection in acute leukemia patients.
• To compare RNA-seq's sensitivity, specificity, and concordance against conventional diagnostic techniques.
• To assess RNA-seq's ability to identify novel or rare fusion genes missed by standard methods.

Main Methods:

• Retrospective analysis of 101 acute leukemia patients diagnosed between September 2022 and September 2023.
• Conventional diagnostics included karyotyping, FISH, and multiplex reverse transcription PCR.
• Whole RNA-seq was performed using the Illumina Stranded mRNA Prep kit.

Main Results:

• RNA-seq detected 52 fusion genes in 51% of patients, with varying rates across leukemia subtypes.
• RNA-seq demonstrated 83.3% sensitivity and 80.8% concordance with conventional diagnostics.
• Twelve fusion genes, including four novel and three rare ones, were identified by RNA-seq in cases negative by conventional methods.

Conclusions:

• Whole RNA-seq is a powerful tool for comprehensive fusion gene detection in acute leukemia.
• Integrating RNA-seq into diagnostic workflows can enhance therapeutic decisions and prognostic assessments.
• This study highlights RNA-seq's potential to improve acute leukemia diagnostics in Korea.