Zeitschrift für Leukämie
Offener Zugang
ISSN: 2329-6917
ISSN: 2329-6917
Irina Shipounova, Natalia Petinati, Alexey Bigildeev, Nina Drize, Tamara Sorokina, Larisa Kuzmina, Elena Parovichnikova, Valery Savchenko
The bone marrow stromal microenvironment that regulates normal hematopoiesis suffers during leukemia development and its treatment. In this study, we examined Multipotent Mesenchymal Stromal Cells (MMSCs) and fibroblast colony-forming units (CFU-F) derived from the Bone Marrow (BM) of 15 adult patients with acute lymphoblastic leukemia (ALL) before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The time points assessed after allo-HSCT were defined by the treatment protocol. The analogous cells obtained from the BM of 64 healthy donors were used as controls. The ability of MMSCs to proliferate, concentration of CFU-F in BM, and gene expression in both cell types were assessed. The data indicate that MMSCs of ALL patients before allo-HSCT did not differ from MMSCs of healthy donors either in cumulative cell production or in gene expression except for SDF1. The SDF1 expression was decreased 2-fold in the MMSCs of ALL patients. The MMSC cumulative cell production from ALL patients was significantly decreased during 1 year after allo-HSCT. The expression level of SDF1 was also downregulated during the observation period. We identified changes in the FGF2 and PDGF signaling pathways. The CFU-F analysis revealed that its concentration in the BM of ALL patients had been profoundly decreased for the whole year after allo-HSCT. This decrease was accompanied by the downregulation of FGFR1 and slight upregulation of differentiation marker gene expression. Thus the number of stromal precursorcells decreased and their ability to regenerate was depressed after allo-HSCT. These changes were accompanied by an increase of more mature precursor cells with reduced proliferative potential.