骨髓增生异常综合征及进展期端粒和端粒酶变化

Telomere and telomerase activity changes in mylodysplatic syndromes with disease progression

目的 探查端粒 (telomere)和端粒酶 (telomerase)在骨髓增生异常综合征 (MDS)患者的MDS期和转化为急性髓性白血病 (AML)期的变化和意义。方法 8例患者 ,18个不同病期的标本 (外周血 11例 ,骨髓 7例 )被获得。Southern杂交放射性同位素探查端粒长度 ;末端重复放大程序(telomeicrepeatamplificationprotocol,TRAP)和定量PCR测定端粒酶。结果 MDS患者的端粒长度 (6 5 8kb± 2 81kb)较年龄匹配的正常人端粒长度 (9 73kb± 0 79kb)明显缩短 (P <0 0 5 )。与正常对照比较 ,8例患者中仅 1例端粒未缩短 ;其余 7例均缩短 ,其中 2例在MDS期尚正常 ,AML期时明显变短 ;另 5例患者在MDS期和AML期端粒均缩短。全部患者均可测得端粒酶 ,AML期的端粒酶活性(36 91± 2 0 5 2 )较MDS期的端粒酶活性 (2 0 49± 11 0 1)明显增加 (P <0 0 5 )。结论 MDS患者的端粒缩短和端粒酶活性增强的现象可能与病情进展有关 。

Objective To investigate the telomere length and telomerase activity changes in mylodysplatic syndromes (MDS) with disease progression in bone marrow and peripheral blood. Methods 18 samples from 8 MDS patients were studied. 5 were RAEB T cases, 2 CMML and 1 RA cases. Telomere length was measured by Southern blot hybridization using the (TTAGGG) 4 probe, and telomerase activity was detected by telomerase repeat amplification protocol (TRAP) and real time quantitative polymerasa chain reactive (PCR). Results The telomere length expressed as the teminal restriction fragmant (TRF). TRF shortening was observed in MDSs patients(6 58 kb±2 81 kb) comparing with that of normal same age Exp TRF(9 73 kb±0 79 kb),( P <0 05). TRF length were significantly shortened from MDS to acute myelogeneouts leukemia(AML)in two cases. Five cases were no change of shortened TRF in both AML and MDS. Only one cases TRF was in the normal range. All cases telomerase activity were expressed and telomerase activity was significantly enhanced from MDS (20 49±11 01) to AML (36 91±20 52), ( P <0 05 ). Conclusion Telomere length shortened and telomerase activity expressed in both MDS and AML. Changes of telomere shortening and telomerase activity enhancement are more significant in AML than those of MDS, which may indicate poor prognosis.