title: 'Low-risk' myelodysplastic syndrome is associated with excessive apoptosis and an increased ratio of pro- versus anti-apoptotic bcl-2-related proteins.
abstract: We performed flow cytometric analysis of CD34+ cell apoptosis in 59 patients with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) secondary to MDS (MDS-AML) using annexin V-FITC, which binds to exposed phosphatidylserine 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 RAEB-t/MDS-AML (16% (2.1-43.2%), P<0.0001). There was no correlation between % apoptosis, Full blood count or cytogenetics in any disease category. Two-colour cytometric analysis of permeabilized CD34+ cells stained with antibodies to Bcl-2, Bcl-X (anti-apoptotic), Bax and Bad (pro-apoptotic), 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 between individual Bcl-2-related proteins differed significantly according to disease subtype (P<0.0005). Our results confirm that CD34+ cell apoptosis was significantly increased in MDS subtypes RA and RARS and fell with disease progression. Early MDS was also associated with a significantly higher CD34+ cell pro- v anti-apoptotic Bcl-2-family-protein ratio than advanced disease. Furthermore, patterns of expression of individual Bcl-2 related proteins differed significantly between different disease categories. However, no correlation between pro- v anti-apoptotic Bcl-2-family-protein ratios and the degree of apoptosis was observed.
authors.affiliation: King's College Hospital and School of Medicine and Dentistry, London.
authors.forename: J E
authors.initials: JE
authors.lastname: Parker
authors.forename: K L
authors.initials: KL
authors.lastname: Fishlock
authors.forename: A
authors.initials: A
authors.lastname: Mijovic
authors.forename: B
authors.initials: B
authors.lastname: Czepulkowski
authors.forename: A
authors.initials: A
authors.lastname: Pagliuca
authors.forename: G J
authors.initials: GJ
authors.lastname: Mufti
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5 / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D018952:Antigens, CD34; D019253:Proto-Oncogene Proteins c-bcl-2