Predictive value of TGF-β1 and SMAD-7 expression at diagnosis for treatment response in low-risk myelodysplastic syndrome

Abstract

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease. Supportive treatments, such as erythropoiesis-stimulating agents (ESAs), are commonly used in patients with low-risk MDS. This study aimed to retrospectively assess the impact of bone marrow Mothers against decapentaplegic homolog 7 (SMAD-7) and transforming growth factor beta 1 (TGF-β1) protein expression on prognosis and response to ESA treatment in patients with low-risk MDS. We retrospectively analyzed patients diagnosed with low-risk MDS at the adult hematology department of Bursa Uludağ University Hospital. A total of 56 patients classified as low or very low risk were included in the study. Immunohistochemical analysis of bone marrow specimens at diagnosis showed that only five patients (9.8%) exhibited low SMAD-7 staining, while 51 patients (90.2%) showed no staining. Regarding TGF-β1 staining, 18 patients (32.1%) demonstrated moderate to high staining, whereas 38 patients (67.9%) exhibited low (36/38) or no staining (2/38). A statistically significant correlation was found between TGF-β1 staining levels and ESA treatment administration (P = 0.011). Additionally, a significant relationship was observed between lower erythropoietin (EPO) levels and moderate to high TGF-β1 staining (P = 0.04). However, when TGF-β1 staining status was compared with first- and third-month treatment responses in patients receiving ESA therapy, no significant difference was detected between groups. These findings suggest that while TGF-β1 alone may not be sufficient to predict ESA treatment response, additional parameters related to the TGF-β/SMAD pathway should be considered. Strong TGF-β1 staining, alongside EPO levels, may influence the decision to initiate ESA therapy.