Smad۳ and Smad۷ Genes Expression in TGF-β Signaling Pathway in Patients with Acute Lymphoblastic Leukemia

Introduction: Acute lymphoblastic leukemia (ALL) is an aggressive hematologic malignancy characterized by the clonal expansion of immature lymphoid blasts in the bone marrow, affecting both children and adults. The transforming growth factor-β/ Smad signaling pathway, a critical tumor-suppressor pathway, is frequently dysregulated in various cancers. This study aimed to investigate the expression levels of Smad۳ and Smad۷ in ALL patients to assess potential dysregulation. Materials and Methods: We analyzed bone marrow and peripheral blood samples from ۵۲ newly diagnosed ALL patients (including ۲۰ pediatrics and ۳۲ adults) and ۱۵ healthy controls. Samples were assessed for morphology, immunocytochemistry, immunophenotyping, and molecular markers. Reverse transcription quantitative real-time polymerase chain reaction was used to evaluate Smad۳ and Smad۷ expression levels. Results: Compared to the control group, ALL leukemia patients exhibited a statistically significant downregulation of Smad۳ and upregulation of Smad۷. The oncogenic role of Smad۷ was more prominent in specific subtypes, with its expression being significantly higher in pediatric ALL compared to adult ALL, and in B-ALL compared to T-ALL. Conclusions: Our findings suggest that decreased Smad۳ (a key receptor-regulated Smad) and elevated Smad۷ (an inhibitory Smad) may contribute to transforming growth factor-β pathway resistance, potentially playing a role in ALL pathogenesis. This study highlights the involvement of Smad dysregulation in patients with ALL, offering insights into molecular mechanisms and potential therapeutic targets. Further research is warranted to validate these findings and explore clinical applications.

کلیدواژه ها:

Acute lymphoblastic leukemia ، Gene expression ، Pediatric leukemia ، SMAD۳ ، SMAD۷ ، Transforming growth factor beta ، کلمات کلیدی: لوسمی لنفوبلاستیک حاد ، لوسمی کودکان ، مسیر سیگنالینگ TGF-β/SMAD ، SMAD۳ ، SMAD۷ ، بیان ژن