Research of 5q deletion influence on hematopoiesis of myelodysplastic syndrome using single-cell RNA sequencing analysis

Abstract

Myelodysplastic syndrome is one of the heterogeneous hematological disorders characterized by cancerous traits. Initially presenting as low-risk, MDS is often difficult to detect due to its subtle symptoms and can progress to severe conditions such as acute myeloid leukemia. A crucial aspect of MDS is clonal expansion, which results from abnormal differentiation. Among the various chromosomal aberrations in MDS, haploinsufficiency due to 5q deletion is one of the most common chromosome aberration. Therefore, we aimed to investigate the relationship between these two aspects by analyzing the transcriptomes of MDS patients with different 5q deletions to understand the impact of 5q deletion on the differentiation process. We analyzed scRNA-seq data to identify the deletion patterns and ratios across different cell types in each patient. Our results showed a high deletion ratio in progenitor cell types, with myeloid lineage cell types also exhibiting a substantial deletion ratio of nearly 40% on average. However, the deletion ratio in lymphoid lineage cell types was notably lower compared to myeloid lineage cell types, averaging less than 20%. This suggests a common impact of 5q deletion on the lymphoid differentiation pathway in MDS patients. Further analysis of gene expression levels in genes located in the 5q region, particularly those involved in differentiation, revealed consistent downregulation of genes such as EGR1, IRF1, and TCF7, which are crucial for lymphoid cell differentiation, in HSCs and LMPPs.