'Low-risk' myelodysplastic syndrome is associated with excessive apoptosisand an increased ratio of pro-versus anti-apoptotic bcl-2-related proteins

We performed flow cytometric analysis of CD34(+) cell apoptosis in 59 patie nts with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) se condary to MDS (MDS-AML) using annexin V-FITC, which binds to exposed phosp hatidylserine on apoptotic cells. Apoptosis was significantly increased in FAB subtypes RA, RARS and RAEB (<10% blasts) (56.5% (15.1-86.5%)) compared to normal controls (18.5% (3.4-33.4%), P<0.0001) and RAEBt/MDS-AML (16% (2. 1-43.2%), P<0.0001). There was no correlation between % apoptosis, Full blo od count or cytogenetics in any disease category. Two-colour cytometric ana lysis of permeabilized CD34(+) cells stained with antibodies to Bcl-2, Bcl- X (anti-apoptotic), Bar and Bad (proapoptotic), demonstrated significantly higher ratios of pro- v anti-apoptotic proteins in early MDS (2.47 (1.19-9. 42) compared to advanced disease (1.14 (0.06-3.32), P = 0.0001). Moreover, using repeated measures of variants (ANOVA), we found that variations betwe en individual Bcl-2-related proteins differed significantly according to di sease subtype (P<0.0005). Our results confirm that CD34(+) cell apoptosis w as significantly increased in MDS subtypes RA and RARS and fell with diseas e progression. Early MDS was also associated with a significantly higher CD 34(+) cell pro-v anti-apoptotic Bcl-2-family-protein ratio than advanced di sease. Furthermore, patterns of expression of individual Bcl-2 related prot eins differed significantly between different disease categories. However n o correlation between pro-v anti-apoptotic Bcl-2-family-protein ratios and the degree of apoptosis was observed.