INVESTIGATING THE IMPACT OF EGCG ON INEFFECTIVE HEMATOPOIESIS IN A MDS MOUSE MODEL

Abstract

Background and aims: Green tea catechins, particularly, epigallocatechin-3-gallate (EGCG), exhibit a range of beneficial effects, like apoptosis and differentiation-promoting effect which can help to counteract the uncontrolled proliferation and impaired differentiation trait of leukemia and myelodysplastic syndrome. This study aims to evaluate the effect of EGCG in vivo in mice model of myelodysplastic syndrome (NHD13 mice). Methods: To assess the effects of EGCG on MDS, 10-week-old female NUP98-HOXD13 mice and their littermate WT mice were treated with EGCG (50 mg/kg/day 5x/week i.p. for 4 weeks) or vehicle. Animals were sacrificed and bone marrow and spleen were obtained to evaluate immune system by flow cytometry and histology analyses. In addition, automated hematological counts and clinical biochemistry parameter analysis were done. Moreover, a 71-year-old man diagnosed with high-risk myelodysplastic syndrome (MSD) with 9% blast presence in the bone marrow, underwent a daily treatment of 800 mg EGCG intake, administered orally. Throughout this period, the patient underwent weekly regular clinical assessments and laboratory studies for monitor any potential toxicities. Additionally, peripheral blood samples were evaluated before and after the treatment to observe any alterations in immune cell composition. Results and discussion: NDH13+ exhibited, before the treatment, a reduction in the number of leukocytes, platelets and hemoglobin levels, which was in line with literature. EGCG treatment ameliorates the hematological parameters, visualized by the increase in the number of leukocytes (monocytes and neutrophils) and platelets; with no signals of toxicity - not morphological features nor enzyme levels changes in the liver. The expansion of Foxp3+ regulatory T cells leads the suppression of host antitumor responses and is a characteristic of progression to aggressive subtypes of the disease. Interestingly EGCG did not alter the percentage/frequency Foxp3+ regulatory T cells (CD4+CD25+ and/or CD4+FOXP3+), as well as the percentage/frequency of immature cells (CD45IntCD34+), in bone marrow and spleen. Our preliminary results showed an increase in extramedullary hematopoiesis in the spleen. One patient treated by EGCG for a month, exhibit reduction of regulatory T cells CD4+CD25+ and CD4+FOXP3+), and increased CD8+ T cells (CD3+CD8+) and natural killer cells (CD16+CD56+) accompanied with an increase of mature leukocytes (monocytes and neutrophils), with no changes in hemoglobin levels and platelets number. Conclusion: Our initial findings indicate that EGCG treatment may reduce ineffective hematopoiesis leading to an improvement of hematological parameters. These results align with the data obtained from one patient with high-risk myelodysplastic syndrome HR-SMD who received EGCG treatment. In summary, EGCG might be a promising adjuvant compound in the treatment of MDS. Further research and clinical studies are warranted to validate and explore its therapeutic benefits fully.