[Impaired expression of genes regulating homeostasis of stem hemopoietic cells in stromal cells of patients with aplastic anemia].
OBJECTIVE
To evaluate expression of genes participating in regulation of hemopoietic stem cells (HSC) in the cells of stromal sublayer of bone marrow long-term cultures in patients with aplastic anemia (AA); to determine effects of parathyroid hormone (PTH) on stromal microenvironment and on its ability to maintain HSC homeostasis.


METHODS
Gene expression in the sublayer of the adherent cells (SAC) was examined with RT-PCt. SAC was for a long time treated with PTH, then their ability to secure survival of early hemopoietic precursors was tested. Changes in the function of stromal cells and expression of some genes were compared in 9 AA patients and 14 donors.


RESULTS
Stromal sublayer of AA patients is characterized by low expression of Ang-1 and VCAM-1 genes and high VEGF expression compared to mean level of healthy donors. PTH stimulates expression of different genes participating in HSC regulation in stromal cells of some patients and improves survival of early hemopoietic hemopoietic precursors on such sublayers.


CONCLUSIONS
AA patients have severe defects in SAC interaction with stroma. In some cases the defects can be partially compensated with application of PTH.
Petrova
T V
TV
Nifontova
I N
IN
Svinareva
D A
DA
Vinogradova
M A
MA
Mikhaĭlova
E A
EA
Drize
N I
NI
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D000803:Angiotensin I / Q000096:biosynthesis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
D004273:DNA, Neoplasm; D010281:Parathyroid Hormone; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D000803:Angiotensin I