Objective: Acute Myeloid Leukaemia (AML) is an aggressive haematological malignancy with poor prognosis, mainly due to its complex interactions with the immune microenvironment. The RHD and RHCE genes, best known for their role in red blood cell biology, are emerging as potential regulators of immune processes. This study aimed to investigate the differential expression of RHD and RHCE in various immune cell types within AML tumour samples and healthy blood samples, utilising large-scale transcriptomic data (TCGA and GTEx).

Materials and Methods: Gene expression analyses were conducted using GEPIA, GEPIA2, and GEPIA2021, which integrate data from TCGA and GTEx. Normalised expression levels of RHD and RHCE were compared between AML tumour and normal blood samples across various immune cell types, including monocytes, macrophages, T cells, and NK cells, using log2(TPM + 1) values.

Results: Both RHD and RHCE were significantly overexpressed in AML tumour samples compared to healthy blood samples across several immune cell populations, including monocytes, macrophages, T cells, and B cells. Notably, RHDwas highly expressed in T cells and monocytes, whilst RHCE showed elevated expression in macrophages and dendritic cells. In contrast, activated NK cells displayed higher RHCE expression in normal blood than in AML tumour samples.

Conclusions: The differential expression of RHD and RHCE in immune cells suggests their potential roles in modulating the immune microenvironment in AML. These findings provide a foundation for future research into the functional implications of RHD and RHCE in leukaemia progression and immune regulation. The study also highlights the utility of GEPIA platforms for comprehensive gene expression analysis in haematological malignancies.