The Clinical And Biological Studies Of Myelodysplastic Syndrome

The clinical and biological studies of 2080 myelodysplastic syndromesin a single center for 30 consecutive years(1984-2013)Objective:To analyse systematically the clinical and biological characteristics of 2080 myelodysplastic syndrome patients in our laboratory from 1984 to 2013 and to reveal the unique features of MDS patient in our area.Methods:1.Conventional cytogenetics were performed to investigated the cytogenetics changes in 2080 MDS patients. All patients were classified according to the FAB criterion, in which, 1493 cases were reclassified according to the WHO(2008) criterion; and 550 patients’ outcomes were evaluated according to the International Prognostic Scoring System, WHO classi?cation–based Prognostic Scoring System(WPSS) and the revised International Prognostic Scoring System(IPSS-R).2.We analysed the clinical, cytogenetic characteristics and survival of 2080 MDS patients by statistical methods.Results :1.According to the FAB criterion: 1040(50.0%) patients with RA, 135(6.5%) patients with RARS, 691(33.2%) patients with RAEB, 145(7.0%) patients with RAEB-t, and 69(3.3%) patients with CMML. The median age was 51 years old(range, 5-93 years old). The ratio of male and female was 1.54. 40.3%(839/2080) patients had clonal chromosome abnormalities, in which 277(13.3%) patients with complexed karyotype. The rate of karyotype abnormalities was higher in RAEB than that in other subtypes. Survival analysis show that the subgroup with RA had a longer median survival duration than the subgroup with RAS, RAEB, RAEB-t, their median survival duration was 50 months, 32 months, 13 months and 16 months, respectively.2.According to the WHO(2008) criterion: 220 patients(14.7%) with RA/RN/RT/RCUD, 75 patients(5.0%) with RARS, 385 patient(25.8%) with RCMD, 14 patient(0.9%) with 5q- syndrome, 282 patients(18.9%) with RAEB-1, 306 patients(20.5%) with RAEB-2, 211 patients(14.1%) with MDS-U. The ratio of male and female was 1.51(898/595) and the median age was 54 years old(range, 6-93 years old). In all patients, the median hemoglobin level was 70g/L(11~167 g/L), the median platelet count was 51.5×109/L(2~1045 ×109/L) and the median WBC count was 2.65×109/L(0.11~52×109/L). The rate of clonal chromosome abnormalities was 42.1%(628/1493), in which 216(14.5%) patients with complexed karyotype. There was statistically significant difference in the rate of chromosomal abnormalities among different subtypes(P<0.01). RA/RN/RT/RCUD had a longer median survival duration than other subgroups, in order of MDS-U, RCMD, RARS, RAEB-1 and RAEB-2.3.Among 2080 patients, 839 patients with clonal chromosome abnormalities. chromosome aberration types mainly uneven anomalies, the most common trisomies or monomer. The most common abnormity was +8. Other aberrations in frequent order was-7/del(7q), del(20q), del(5q), and so on.4.Stastistics for survival, 550 patients’ outcomes were evaluated according to the IPSS, WPSS and IPSS-R. The results show the IPSS, WPSS and IPSS-R score were significantly affected OS(P<0.001). When comparing the prognostic value of the IPSS, WPSS, and IPSS-R, using the Cox regression model, a significantly higher predictive power for OS became evident for the IPSS-R, compared with the IPSS and WPSS.Conclusion:1.In our study, the MDS patients showed the unique clinical and biological features. We found that the characteristics of cytogenetics has significant differences from western MDS patients. The most common abnormity was +8. Other aberrations in frequent order was-7/del(7q), del(20q), del(5q), and so on.2.IPSS-R is a powerful tool in MDS survival analysis.WT1 gene expression in myelodysplastic syndromes and its clinicalImplicationObjective:To reveal WT1 gene expression in MDS and its clinical implication,we measured the level of WT1 gene expression in 113 newly diagnosed myelodysplastic syndromes.Methods:1.We measured the transcript levels of the WT1 gene and ABL gene in 113 newly diagnosed MDS patients by real-time quantitative RT-PCR. The WT1 transcripts were normalized with respect to the number of ABL transcripts and expressed as WT1 or copy numbers every 104 copies of ABL. In this study, a value of 300copies/10000 abl copies was set as the cut-off value for WT1 m RNA expression.2.We analyzed whether the levels of WT1 m RNA expression were associated with clinical characteristics( IPSS score, IPSS-R score and MDS subtype in the FAB and WHO classifications), overall survival, and time of event-free survival by statistical methods. Thereby discuss its relationship with disease progression and clinical significance.Results:1.There are different levels of WT1 gene expression in MDS patients. Forty-four(50/113) percent of all patients with high WT1 levels and it was highly correlated with the type of MDS, was much higher with the disease progression. The positive rates of WT1 expression in RAEB and RAEB-t were higher than those in RA and RAS in FAB classifacation. The expression level was gradually increased from RCUD to RCMD and RAEB-1 and RAEB-2 in WHO classification.2.The expression of WT1 gene was highly correlated with the IPSS score, and was tended to increase with disease stage progression.3.Overall survival and event-free survival differed significantly in accordance with the increased WT1 transcripts in univariate analyses(p=0.038 and P=0.003, respectively). Multivariate analysis also revealed that higher WT1 and the revised-IPSS category was an independent predictive marker for EFS(P=0.031 and P<0.001, respectively).4.It is noteworthy that the WT1 overexpression showed a significant effect on EFS in patients with bone marrow blasts less than 5%(P=0.016).Conclusion:There are different levels of WT1 gene expression in MDS patients, and they tended to increase with disease stage progression. It can be used for risk assessment and monitor of disease progression and therapeutic effects in MDS patients.