Bcl-2 and Bcl-x expression in the CD34+ cells of aplastic anaemia patients: relationship with increased apoptosis and upregulation of Fas antigen.
Aplastic anaemia (AA) is a syndrome of haemopoietic failure involving increased apoptosis in stem cells. AA CD34+ cells often have upregulated Fas antigen, but this does not explain the increased apoptosis in all patients. To examine whether abnormal expression of the apoptotic modulators Bcl-2 and Bcl-x is involved in increased apoptosis in the CD34+ cells of patients, we examined cells from 19 AA patients and 18 normal controls by triple staining for CD34, Bcl-2 or Bcl-x, together with 7-amino actinomycin D to determine viability or with staining for Fas antigen. We confirmed increased apoptosis of CD34+ cells in patients. All CD34+ cells in patients and controls expressed Bcl-2 and Bcl-x with no significant difference between the groups. In patients, viability of CD34+/Bcl-2hi cells was similar to that of CD34+/Bcl-2lo cells, but CD34+/Bcl-xhi cells were significantly more viable than CD34+/Bcl-xlo cells. CD34+ cells from AA patients expressed upregulated Fas antigen, but this did not correlate with Bcl-2 or Bcl-x expression. These results suggest a more significant role for Bcl-x as an anti-apoptotic regulator in CD34+ cells in AA than Bcl-2. The induction of death by Fas antigen may bypass the anti-apoptotic effect of Bcl-2 and Bcl-x in CD34+ cells in AA.
Ismail
M
M
Department of Haematology, St. George's Hospital Medical School, London, UK.
Gibson
F M
FM
Gordon-Smith
E C
EC
Rutherford
T R
TR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000276:immunology / Q000378:metabolism*; D018952:Antigens, CD34; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051020:bcl-X Protein; D019014:fas Receptor / Q000378:metabolism*
D018952:Antigens, CD34; C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor