Abnormal intracellular level of Bax in CD3+ cells from untreated B-cell chronic lymphocytic leukemia patients.
B-cell chronic lymphocytic leukemia (B-CLL) is a lymphoproliferative disease caused by impaired apoptosis regulation that leads to an abnormal survival and an accumulation of B-lymphocytes. Anti-apoptotic Bcl-2 and proapoptotic Bax proteins are involved in the highly regulated mechanism of cell death. Bax and Bcl-2 intracellular levels were analyzed both in CD19+ and CD3+ cells from 28 B-CLL de novo patients and compared with cells from healthy donors. Our results were expressed as a ratio (Bax/Bcl-2) obtained by dividing Bax mean fluorescence intensity (MFI) and Bcl-2 MFI; obviously, a lower ratio is associated with an anti-apoptotic status, while a higher index correlates to apoptosis activation. In CD19+ B-CLL cells, the Bax/Bcl-2 ratio was lower than in the CD19+ normal counterpart (1.3 versus 3.51; P<.05), mainly due to a Bcl-2 over expression (17.65 versus 9.02; P<.001). In CD3+ cells from B-CLL patients, the Bax/Bcl-2 ratio was lower than in normal CD3+ cells (7.89 versus 8.96; P<.005), most importantly as a result of Bax suppression (77.22 versus 96.63; P<.001). These study data show an apoptosis inhibition not only in CD19+ cells, but also in CD3+ cells, suggesting a pivotal role of T-cells in B-CLL pathogenesis.
Scamardella
F
F
Department of Clinical Pathology, AO Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
Maconi
M
M
Albertazzi
L
L
Gamberi
B
B
Gugliotta
L
L
Brini
M
M
D000328:Adult; D000368:Aged; D018941:Antigens, CD19; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D017252:CD3 Complex; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D018941:Antigens, CD19; D017252:CD3 Complex; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein