Upregulation of S100A6 and its relation with CD34+ cells apoptosis in high-risk myelodysplastic syndromes patients

Heliyon. 2023 Aug 5;9(8):e18947. doi: 10.1016/j.heliyon.2023.e18947. eCollection 2023 Aug.

Abstract

Objectives: Myelodysplastic syndromes (MDS) are a group of myeloid malignancies characterized by peripheral blood cytopenia and hematopoietic dysplasia that often progress to acute myeloid leukemia (AML). Increased apoptosis of normal hematopoietic cells and decreased apoptosis of malignant clonal hematopoietic cells in patients with MDS is some of the mechanisms leading to ineffective hematopoietic cells in the bone marrow. S100 calcium-binding protein A6 (S100A6) is upregulated in many malignancies. The overexpression of S100A6 in these malignancies has been associated with proliferation, migration, and invasion phenotypes in cancer cells, and we aimed to investigate the expression of S100A6 in CD34+ cells and the relationship between S100A6 expression and apoptosis of CD34+ cells in high-risk patients with MDS.

Methods: We measured S100A6 mRNA expression in bone marrow (BM) CD34+ cells from high-risk patients with MDS using RT-PCR. Next, we examined S100A6 expression in CD34+ cells using flow cytometry. We also analyzed the correlation between CD34+ cell apoptosis and S100A6 expression in high-risk patients with MDS.

Results: Our data showed increased S100A6 mRNA expression in CD34+ cells in patients with MDS (1.05 ± 0.69 vs. 0.17 ± 0.12; P<0.01). The expression of S100A6 in BM CD34+ cells also increased (58.40 ± 13.18 vs. 45.83 ± 15.01). The expression of S100A6 in CD34+ cells and apoptosis of CD34+ cells were negatively correlated in patients (r = -0.75; P < 0.01).

Conclusions: Collectively, S100A6 may be a potential marker of CD34+ cells in high-risk patients with MDS and may participate in the pathological behaviors of CD34+ cells, such as evasion of apoptosis. Thus, S100A6 may be a potential target for eliminating minimal residual disease.

Keywords: Apoptosis; CD34+ cells; Myelodysplastic syndromes; S100A6.