‘Low‐risk’ myelodysplastic syndrome is associated with excessive apoptosis and an increased ratio of pro‐ versus anti‐apoptotic bcl‐2‐related proteins

• Published in: British journal of haematology Vol. 103; no. 4; pp. 1075 - 1082
• Main Authors: PARKER, J. E, FISHLOCK, K. L, MIJOVIC, A, CZEPULKOWSKI, B, PAGLIUCA, A, MUFTI, G. J
• Format: Journal Article
• Language: English
• Published: Oxford, U.K. and Cambridge, USA Blackwell Science Ltd 01-12-1998; Blackwell
• Subjects: Acute Disease; acute myeloid leukaemia; Adult; Aged; Aged, 80 and over; Annexin A5 - metabolism; annexin V; Antigens, CD34 - metabolism; apoptosis; Apoptosis - physiology; Bcl‐2; Biological and medical sciences; Female; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; Leukemia, Myeloid - metabolism; Leukemia, Myeloid - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; myelodysplastic syndrome; Myelodysplastic Syndromes - metabolism; Myelodysplastic Syndromes - pathology; Proto-Oncogene Proteins c-bcl-2 - metabolism; Human; Flow cytometry; Fluorescent labelling; Cell death; Pathogenesis; Gene product; C-Onc gene; Genetics; Malignant hemopathy; Myelodysplastic syndrome; Protooncogene; Apoptosis
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.1998.01114.x

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.