[Apoptosis and proliferative activity of bone marrow cells in patients with aplastic syndromes as evidenced by trephine biopsy].
OBJECTIVE
To clarify the effect of cyclosporin A (CSA) on the apoptosis and proliferative activity of bone marrow cells in patients with aplastic syndromes by trepanobiopsy evidence.


METHODS
The TUNEL immunohistochemical assay was used to study apoptosis of bone marrow cells in the histological specimens from 24 patients: 8 with refractory anemia (RA), 8 with acute small-proportion leukemias [RA with excessive blasts (RAEB) + RAEB in transformation (RAEBt)], 3 with acute non-lymphoblastic leukemia (ANLL), 5 with lymphogranulomatosis (LGM). Control apoptosis examination was made in 10 patients treated with CSA. The proliferative activity of bone marrow cell was evaluated by bone marrow histological specimens from 10 patients (8 patients with RA and 2 with RAEB + RAEBt) at the onset of disease and during CSA therapy in the immunohistochemical test with primary nuclear antigen Ki-67 antigen antibodies. Changes in the proliferative activity and degree of apoptosis of bone marrow cells were assessed in relation to the cellularity detectable by the histological specimens.


RESULTS
Patients with RA showed an increase in bone marrow cell apoptosis to 25.375 +/- 6.874 (-10.8 +/- 5.122 and 8.333 +/- 5.84 in controls and ANLL patients, respectively). The cells of hemopoiesis and stromal microenvironment are in the process of cell death. Higher bone marrow cellularity is observed in CSA-treated patients at clinical and hematological remission, which is followed by rises in the index of proliferation and the degree of apoptosis.


CONCLUSIONS
The clinical effect of CSA in patients with aplastic syndromes is induced by its direct or mediated stimulating effect on pluripotent stem cells of hemopoiesis, by increasing bone marrow cellularity at the expense of clonal and/or normal hemopoiesis.
Kokhno
A V
AV
Savchenko
V G
VG
Parovichnikova
E N
EN
Kharazishvili
D I
DI
Sokolovskaia
A A
AA
Lukashina
M I
MI
Baryshnikov
A Iu
AIu
D000208:Acute Disease; D000753:Anemia, Refractory / Q000188:drug therapy*; D017209:Apoptosis / Q000187:drug effects; D001706:Biopsy; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007938:Leukemia / Q000188:drug therapy*; D008962:Models, Theoretical
D007166:Immunosuppressive Agents; D016572:Cyclosporine
Apoptoz i proliferativnaia aktivnost' kletok kostnogo mozga u bol'nykh s aplasticheskimi sindromami po dannym trepanobiopsii.