Whole transcriptome sequencing reveals differences in the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia.

[OBJECTIVES] Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are closely related hematologic malignancies. However, the transcriptomic distinctions between them are not fully elucidated. This study aimed to identify transcriptional differences between MDS and AML using whole transcriptome sequencing to provide a theoretical basis for improved diagnosis and treatment.

[METHODS] Whole transcriptome sequencing was conducted to profile the expression of mRNAs and non-coding RNAs in MDS and AML samples. Subsequent bioinformatic analyzes were performed to identify differentially expressed genes and their potential functional roles.

[RESULTS] Comprehensive sequencing revealed 1926 differentially expressed mRNAs, 80 miRNAs, 1553 lncRNAs, and 1635 circRNAs between MDS and AML. Functional enrichment analysis indicated that these differentially expressed genes are predominantly involved in key pathways such as ferroptosis, immune response, and cell cycle regulation. Further investigation highlighted a significant association of differentially expressed lncRNAs and circRNAs with the ferroptosis pathway. Key molecules implicated in ferroptosis included AQP3, ALOX5, ADAM23, STK11, AIFM2, hsa-miR-4433b-3p, hsa-miR-1307-3p, hsa-miR-23a-5p, and hsa-miR-3916.

[DISCUSSION] The distinct transcriptomic profiles uncovered in this study reveal critical molecular differences in the pathogenesis of MDS and AML. The strong enrichment of ferroptosis-related pathways, mediated by specific coding and non-coding RNAs, suggests a pivotal role for this biological process in disease development and progression from MDS to AML.

[CONCLUSION] Our study identified crucial genes and non-coding RNAs linked to ferroptosis, implicating their potential roles in MDS and AML pathogenesis and offering valuable candidate targets for future research.