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

ABSTRACT

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