Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality...

Area of Science:

• Hematology
• Oncology
• Cell Biology

Background:

• Pediatric myelodysplastic syndrome (MDS) is a heterogeneous clonal hematopoietic stem cell disorder.
• Evidence suggests the bone marrow microenvironment plays a role in adult MDS.
• The role of mesenchymal stromal cells (MSCs) in pediatric MDS remains less understood.

Purpose of the Study:

• To investigate the characteristics of bone marrow-derived MSCs from pediatric MDS patients.
• To compare MSCs from pediatric MDS patients with those from healthy pediatric controls.
• To identify molecular differences in MSCs that may contribute to pediatric MDS pathogenesis.

Main Methods:

• Expansion of MSCs from bone marrow of 17 pediatric MDS patients (10 with refractory cytopenia of childhood [RCC] and 7 with advanced MDS) and 10 pediatric controls.
• Assessment of MSC phenotype, differentiation capacity, immunomodulatory capacity, and hematopoietic support.
• Deep-SAGE mRNA expression analysis to identify differentially expressed genes.

Main Results:

• No significant differences in MSC phenotype, differentiation, immunomodulation, or hematopoietic support between pediatric MDS and control groups.
• Increased IL-6 expression observed in MSCs from RCC and RAEB(t)-MDS patients.
• RCC-MDS MSCs showed increased DKK3 expression; RAEB(t)-MDS MSCs exhibited increased CRLF1 and decreased DAPK1 expression, patterns associated with malignant transformation.

Conclusions:

• Altered mRNA expression profiles in MSCs from pediatric MDS patients suggest a role for the microenvironment in disease pathogenesis.
• The molecular signatures in pediatric MDS MSCs differ from those reported in adult MDS MSCs, supporting distinct disease entities.
• Further investigation into these altered pathways may identify novel therapeutic targets for pediatric MDS.