The dynamic interaction of pediatric ALL cells and MSCs: influencing leukemic cell survival and modulating MSC β-catenin expression


ÖZDEMİR SANCI T., ÇORUMLUOĞLU İ., Köksal Y., ÇAYLI S., ÖZBEK N. Y., ÖZGÜNER H. M.

Histochemistry and Cell Biology, cilt.163, sa.1, 2025 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 163 Sayı: 1
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1007/s00418-025-02353-w
  • Dergi Adı: Histochemistry and Cell Biology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, CINAHL, EMBASE, MEDLINE
  • Anahtar Kelimeler: Acute lymphoblastic leukemia, Bone marrow microenvironment, Bone marrow mesenchymal stromal cells, Co-culture, Leukemic blast, beta-catenin
  • Sağlık Bilimleri Üniversitesi Adresli: Evet

Özet

Bone marrow mesenchymal stromal cells (BM-MSCs) are integral components of the bone marrow microenvironment, playing a crucial role in supporting hematopoiesis. Recent studies have investigated the potential involvement of BM-MSCs in the pathophysiology of acute lymphoblastic leukemia (ALL). However, the exact contribution of BM-MSCs to leukemia progression remains unclear because of conflicting findings and limited characterization. In this study, we compared BM-MSCs derived from pediatric ALL patients with those from matched healthy donors (HDs). Our results indicate that while both ALL-MSCs and HD-MSCs meet the criteria established by the International Society for Cellular Therapy, they exhibit significant differences in proliferation and differentiation capacity. ALL-MSCs displayed markedly lower proliferation rates and reduced osteogenic/adipogenic differentiation potential compared to HD-MSCs. Furthermore, co-culture experiments revealed that MSCs enhance the survival of leukemic blasts through both soluble factors and direct cell-cell interactions, underscoring their anti-apoptotic properties. Importantly, our findings demonstrate that interactions with leukemic cells activate the Wnt/β-catenin signaling pathway in MSCs, suggesting a potential target for therapeutic intervention. Overall, this study enhances our understanding of the role of BM-MSCs in leukemia and highlights β-catenin as a promising target for future therapies.