Cytogenetic Features Of Primary Myelodysplastic Syndromes And Clinical Significance

ObjectiveTo investigate the cytogenetic features of primary myelodysplastic syndromes(MDS) in Chinese adult patients.MethodsThree hundred and fifty-one adult patients with primary MDS were retrospectively analyzed for their chromosomal abnormalities by karyotyping.ResultsTwo hundred and thirty-seven cases(67.5%) demonstrated karyotypic abnormalities, including 99 with copy number changes alone(41.7%),70 with structural abnormalities alone(29.5%),and 68 with both of these changes(28.8%).In addition,among the 237 patients with chromosomal abnormalities,130 cases(54.8%) showed single abnormality,54 cases(22.8%) showed double abnormalities and 53 cases(22.4%) showed complex abnormalities(more than two independent aberrations).Four cases(1.7%) were multiploid. Aneuploidy or anomaly of chromosomal arm were detected across all of the 24 chromosomes and the aberrations frequently seen were +8,-20/20q-,-7/7q-,-5/5q-,-18, -11/11q-/,+21,-Y,-21,-10,-16,-22,+9,del(12)(p12) in order.Overall,the frequency of -5/5q-/del(5)(q13-33) was 5.1%in these Chinese MDS patients,which was lower than that in the MDS patients of western countries(8.7-23.4%),and the incidence of 5q-syndrome was only 0.3%in Chinese MDS patients.On the other hand,the frequencies of trisomy 8 (19.1%) and -20/20q-/del(20)(q11-13)(9.4%) were higher than those in western countries (1.2-7.0%and 2.0-3.5%,respectively).Chromosomal translocations were also detected in 31 cases(13.1%) including 12 rare translocations that have not been reported in MDS patients before.In addition,i(17)(q10)was detected in nine cases(3.8%),of which six cases only had this single abnormality.According to the IPSS chromosomal prognostic classification,the incidence of poor-risk karyotypes increased in the advanced WHO subtypes(p＜0.001).ConclusionTogether,we detected the unique cytogenetic features of chromosomal abnormalities. ObjectiveTo investigate the impact of RAD51_G135C,XRCC3_C241T,GSTM1 and GSTT1 genotypes on the myelodysplastic syndromes(MDS) susceptibility and chromosomal abnormalities of MDS.MethodsRAD51_G135C,XRCC3_C241T,GSTT1 and GSTM1 genotypes were detected in 381 adult patients with de novo MDS and 443 healthy controls with comparable age and gender by PCR-RFLP or multi-PCR.ResultsThere was a significant difference of the incidence of RAD51G135C C/C genotype between MDS patients and controls(6.9%vs.3.6%,p=0.037).The odds ratio of this genotype for MDS risk was 2.01(p=0.037,95%CI 1.03～3.91),which was more significant in the multi-factor analysis including age and gender.RAD51G135C C/C genotype remained independently associated with risk of MDS when the joint effect of other genes were considered(p=0.005,OR=2.61,95%CI 1.34～5.11).Moreover,in individuals with normal chromosomal karyotypes,the incidence of RAD51G135C C/C genotype was higher than that in healthy controls(9.9%vs.3.6%). The odds ratio for risk of the normal karyotypic group was 2.92.In individuals with complex chromosomal abnormalities(at least 3 abnormal karyotypes), the incidence of GSTT1 null genotype was higher than in controls.The odds ratio for risk of the complex karyotypic MDS was elevated to 4.79,which was still significant as consideration of age and gender(p=0.009,OR=3.96,95%CI 1.42～11.10).Interestingly, the 5 case of -5/5q- were all with GSTM1 null genotypes.Furthermore,the multi-factor analysis including age,gender,occupational risk factor,non-occupationl risk,WHO subgroups and genotypes showed no significant association between any genotype and chromosomal abnormality in MDS. ConclusionRAD51_G135C C/C genotype is the genetic susceptible factor for Chinese adult patients with primary MDS.XRCC3_C241T genotype and null genotype of GSTT1 or GSTM1 were not independently associated with the occurrence of MDS.RAD51_G135C C/C genotype was relative to MDS with normal karyotype while GSTT1 was relative to MDS with complex abnormal karyotype.Genes in the pathway of DNA DSBs repair and toxin metaboly affected the pathogenesis of MDS in which both genetic factors and environmental factors were involved. ObjectiveTo investigate the prognostic significance of chromosomal karyotype in patients with primary myelodysplastic syndromes(MDS).MethodsOne hundred and sixty-four adult patients with valid results of chromosomal karyotype and successfully followed up were retrospectively analyzed.ResultsAmong the 164 patients,82 died.The median follow-up time was 19(1-138) months and the median survival was 36 months.2-year survival was 60%and 5-year survival was 42%.One hundred and thirteen cases(68.9%) demonstrated karyotypic abnormalities.Of those,45 showed single abnormality.As isolated abnormalities,there were 13 cases with +8,7 cases with -20/20q-,4 cases with -5/5q-,one case with -Y and 6 cases with i(17)(q10),which were recurrently seen in MDS.When it came to aberrance involved chromosomal 7,24 cases were detected either single or together with other abnormalities. According to WPSS chromosomal prognositic classification,the median OS of patients with good,intermediate and poor-risk cytogenetic subgroup were 57(95%CI 37-77), 37(95%CI 20-54),12(95%CI 6-17) months,respectively(p＜0.001).According to NN-AN-AA classification of karyotype,the median OS of patients with NN,AN,AA were 59(95%CI 48-71),37(95%CI 14-60),23(95%CI 11-34) months,respectively(p =0.022).In patients with very low-risk,low-risk,intermediate-risk,high-risk and very high-risk stratified by WPSS,2-year survival were 100%,96%,81%,38%and 14%, respectively;5-year survival were 100%,83%,54%,20%and 0,respectively(p＜0.001).ConclusionChromosomal karyotype is of great importance in revealing prognosis to achieve individual therapy in MDS.In addition,WPSS based on WHO classification was adapted to prognostic determination in Chinese patients with MDS.