title: CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins.
abstract: CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) are distinguished from other MDS cells and from normal hematopoietic cells by their pronounced expression of apoptotic markers. Paradoxically, trisomy 8 clones can persist in patients with bone marrow failure and expand following immunosuppression. We previously demonstrated up-regulation of c-myc and CD1 by microarray analysis. Here, we confirmed these findings by real-time polymerase chain reaction (PCR), demonstrated up-regulation of survivin, c-myc, and CD1 protein expression, and documented comparable colony formation by annexin(+) trisomy 8(-) CD34(+) and annexin(-) CD34 cells. There were low levels of DNA degradation in annexin(+) trisomy 8 CD34 cells, which were comparable with annexin(-) CD34 cells. Trisomy 8 cells were resistant to apoptosis induced by gamma irradiation. Knock-down of survivin by siRNA resulted in preferential loss of trisomy 8 cells. These results suggest that trisomy 8 cells undergo incomplete apoptosis and are nonetheless capable of colony formation and growth.
authors.affiliation: National Heart Lung and Blood Institute, Bethesda, MD 20892, USA. sloande@nhlbi.nih.gov
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Sloand
authors.forename: Loretta
authors.initials: L
authors.lastname: Pfannes
authors.forename: Gubin
authors.initials: G
authors.lastname: Chen
authors.forename: Simant
authors.initials: S
authors.lastname: Shah
authors.forename: Elena E
authors.initials: EE
authors.lastname: Solomou
authors.forename: John
authors.initials: J
authors.lastname: Barrett
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D017302:Annexins / Q000378:metabolism; D018949:Antigens, CD1 / Q000235:genetics; D018952:Antigens, CD34 / Q000378:metabolism*; D017209:Apoptosis / Q000528:radiation effects; D015415:Biomarkers; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D000077022:Survivin; D013997:Time Factors; D014314:Trisomy / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D017302:Annexins; D018949:Antigens, CD1; D018952:Antigens, CD34; C107489:BIRC5 protein, human; D015415:Biomarkers; D051034:Inhibitor of Apoptosis Proteins; C489427:MYC protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000077022:Survivin; D004247:DNA