Researchers found a link between exposure to a soluble CD40 ligand (sCD40L) and expression of tumor necrosis factor a (TNFa) in bone marrow mononuclear cells (BMMCs) from patients with myelodysplastic syndrome (MDS). These findings were recently reported in the journal Stem Cell Investigation.
In this cross-sectional study based in Indonesia, BMMCs were isolated from 15 patients with MDS and 8 control subjects with lymphoma. Cells were exposed to a recombinant human soluble CD40 ligand (rh-sCD40L) in order to assess any effect on the expression of TNFa, which is a proapoptotic cytokine. The researchers evaluated TNFa expression through analyses of messenger RNA and protein, including quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay techniques.
All patients with MDS in this study had some level of cytopenia, with 1 cytopenia in 1 patient, bicytopenia in 7 patients, and pancytopenia in 7 patients. Risk status using the International Prognostic Scoring System-Revised was variable across the population of patients with MDS, ranging from very low risk to very high risk. Patients with MDS had a mean age of 58.9 years and showed a range of bone marrow morphologies.
The researchers observed a statistically significant increase in TNFa mRNA in conjunction with exposure to rh-sCD40L. For MDS BMMCs, exposure to rh-sCD40L was associated with a mean 3.32-fold increase in TNFa mRNA, compared to the level of expression in cells that were not exposed to this agent (P =.047).
TNFa protein was measured in the supernatant media of samples following exposure to rh-sCD40L. In media with MDS cells, the level of TNFa was 44.44 pg/mL, compared with 4.85 pg/mL in media with control cells (P =.018). Prior to being exposed to rh-sCD40L, the MDS and control cells had shown similar levels of TNFa.
Supernatant media with MDS cells exposed to rh-sCD40L also showed a higher mean level of TNFa (44.46 pg/mL) than media did with MDS cells that were not exposed (14.12 pg/mL; P <.05).
“This study has shown that sCD40L has a role in inducing the synthesis of the proapoptotic cytokine TNFα within the bone marrow mononuclear cells of MDS patients,” the researchers concluded in their report.
Iriani A, Setiabudy RD, Kresno SB, et al. Expression of mRNA TNFα and level of protein TNFα after exposure sCD40L in bone marrow mononuclear cells of myelodysplastic syndromes. Stem Cell Investig. 2021;8:6. doi:10.21037/sci-2020-025