Author/Authors :
Youssef, Soha R Ain Shams University - Faculty of Medicine - Department of Clinical Pathology, Egypt , Ismail, Manal M Ain Shams University - Faculty of Medicine - Department of Clinical Pathology, Egypt , Abd EL Wahed, Essam Ain Shams University - Faculty of Medicine - Departments of Clinical Pathology and Internal Medicine, Egypt , El Desokey, Hossam Ain Shams University - Faculty of Medicine - Departments of Clinical Pathology and Internal Medicine, Egypt , Abd EI Aziz Ghanoum, Randa National Heart Institute, Egypt
Abstract :
The essence of MDS pathogenesis is damage of CFU with numerous reports implicating apoptosis.While low risk MDS showed enhanced intramedullary apoptosis, high risk MDS was associated with cellular proliferation. Specific cytogenetic abnormalities strongly correlate with prognosis and survival with patients having trisomy 8 being of intermediate prognosis. However, leukemic transformation is also common and its mechanism remains undetermined. This study aims to correlate the cytogenetic and cellular apoptotic/anti-apoptotic status of high risk MDS patients to their capacity for colony formation, response to therapy and survival. In this work Ninteen newly diagnosed high risk MDS patients and ten hematologicaly free subjects were studied for cellular apoptosis of bone marrow progenitors using tri-color flow cytometric quantification of CD34+/Annexin+/PT cells. Presence of cytogenetic abnormalities was detected in patients using conventional cytogenetic analysis (CCA) and fluorescence in situ hybridization (FISH), while bone marrow mononuclear cells (BMMNC) Survivin expression was evaluated using im munocytochemical examination ofbone marrow cytospin preparations. The capacity for hematopoietic colony formation was performed using long term stem cell cultures. The patients were then treated according to guidelines recommendations and followed up for a mean of 24 months.High risk MDS cases showed significantly higher percent of both apoptotic CD34+/Annexin+/PT 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+/PT cells and capacity for colony formation. The latter was comparable in trisomy 8+ cases to controls while being significantly lower in trisomy 8- MDS patients. Better response to therapy and longer survival in trisomy 8+ cases was observed but was not statistically significant. The results of this work 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. This data imply the feasibility of using these markers as part of the routine diagnostic workup of MDS patients to define new molecular targets of therapeutic significance and provide the rationale for trying relevant new immunotherapies.
