Bcl‐2 and Bcl‐x expression in the CD34+ cells of aplastic anaemia patients: relationship with increased apoptosis and upregulation of Fas antigen

• Published in: British journal of haematology Vol. 113; no. 3; pp. 706 - 712
• Main Authors: Ismail, M., Gibson, F. M., Gordon‐Smith, E. C., Rutherford, T. R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science, Ltd 01.06.2001; Blackwell; Blackwell Publishing Ltd
• Subjects: Adolescent; Adult; Aged; Anemia, Aplastic - immunology; Anemia, Aplastic - metabolism; Antigens, CD34; aplastic anaemia (AA); Apoptosis; bcl-X Protein; Bcl‐2/Bcl‐x; Biological and medical sciences; Bone Marrow Cells - metabolism; Case-Control Studies; CD34+ cells; Child; Fas antigen; fas Receptor - metabolism; Female; Flow Cytometry; Hematologic and hematopoietic diseases; Hematology; Humans; Immunophenotyping; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Proto-Oncogene Proteins c-bcl-2 - metabolism; Human; Pathogenesis; Stem cell; C-Onc gene; Aplastic anemia; Hematopoietic cell; Hemopathy; Gene expression; Protooncogene; Apoptosis
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2001.02810.x

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.