Growth advantage of CD34+ cells in trisomy 8 high-risk myelodysplastic syndrome despite enhanced apoptotic signals

This study examined haematopoietic stem cells of 19 high-risk cases of myelodysplastic syndrome [MDS] for apoptotic and anti-apoptotic signals and cellular proliferation and correlated these with clinical and cytogenetic subtypes, particularly trisomy 8. The aim was to identify cellular and cytogenetic markers of prognostic relevance to survival of high-risk MDS cases. High-risk MDS cases had a significantly higher percentage of apoptotic CD34+ cells and anti-apoptotic survivin+ cells than controls, particularly for trisomy 8 cases. Trisomy 8+ cells showed a significant positive correlation with apoptotic CD34+ cells and capacity for colony formation. The latter was significantly lower in trisomy-8-negative cases than normal controls, while that of trisomy 8 cases was comparable to controls. Our results suggest that although trisomy 8 cells are in a pro-apoptotic state, they are checked by the enhanced expression of anti-apoptotic signals which provide them with their proliferative advantage

Growth advantage of CD34+cells in trisomy 8 high risk mids cases despite enhanced apoptotic signals

The essence of myelodysplastic syndrome [MDS] pathogenesis is damage of colony forming unit [CFU]with numerous reports implicating apoptosis. While low risk MDS showed enhanced intramedullary apoptosis, high risk MDS was associated with cellular proliferation giving the abnormal clone a growth advantage. Ninteen high risk MDS patients were studied for cellular apoptosis of bone marrow progenitors using tn-color flow cytometric quantification of CD34/Annexin/PU cells. Presence of cytogenetic abnormalities was detected using conventional analysis and FISH while bone marrow mononuclear cells' [BMMNC] survivin expression was evaluated using immunocytochemical examination of bone marrow cytospin preparations. The capacity for hematopoietic colony formation was performed using long term stem cell cultures. High risk MDS cases showed significantly higher percent of both apoptotic CD34/Annex1n*/PI cells and anti-apoptotic survivin cells compared to controls with significantly higher percent among trisomy 8 cases. Trisomy 8 cells showed a significant positive correlation with percent of apoptotic CD34/Annexin/PI cells and capacity for colony formation. The latter was significantly lower in MDS patients negative for trisomy 8 as compared to normal controls, while that of trisomy 8 cases was comparable to controls. Although trisomy 8 cells are in a pro-apoptotic state, they are checked by the enhanced expression of antiapoptotic signals which provide them with their proliferative advantage