Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Therapy-related leukemia or myelodysplasia (t-leuk/MDS) is a serious problem that is increasing in frequency. We studied the clinical characteristics of 96 patients (pts) with a mean age of 48 years, and analyzed the molecular parameters that could predispose to t-leuk/MDS. Hematological malignancies were the most common primary (53%), followed by breast and ovarian cancer (30% combined). The mean latency until the development of t-AML was 45.5 months. Median survival was 10 months. Cytogenetics was abnormal in 89% of pts. FLT3 internal tandem duplications were found in six of 41 (14.6%) pts, of whom four had an abnormal karyotype. Analysis of drug metabolism and disposition genes showed a protective effect of the CYP3A4 1*B genotype against the development of t-leuk/MDS, whereas the CC genotype of MDR1 C3435T and the NAD(P)H:quinone oxidoreductase1 codon 187 polymorphism were both noncontributory. Microsatellite instability (MSI) analysis using fluoresceinated PCR with ABI sequence analyzer demonstrated that 41% of pts had high levels of MSI in four or more of 10 microsatellite loci. Immunohistochemistry demonstrated reduced expression of MSH2 and MLH1 in 6/10 pts with MSI as compared to 0/5 of pts without MSI. In conclusion, genetic predisposition as well as epigenetic events contribute to the etiology of t-AML/MDS.
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PMID:Therapy-related leukemia: clinical characteristics and analysis of new molecular risk factors in 96 adult patients. 1616 58

The aim of the present study is to evaluate the frequency of C609T polymorphism in the NQO1 (NAD(P)H) quinon oxydoreductase) gene and its relation to cytogenetic abnormalities in patients with Myelodysplastic Syndrome (MDS). The study group consisted of 80 patients MDS with 13 of them in the pediatric age group. The frequency of the NQO1 gene polymorphism was compared with a healthy control group involving 423 individuals. Cytogenetic abnormalities were detected in 43 patients (54%). In patients with MDS the overall frequency of the C609T polymorphism was not different than controls. Also, although the frequency of the C609T polymorphism was higher in patients with secondary MDS (sMDS) (OR: 1.893, 95% CI: 0.840-4.265, p=0.238) , 5/del(5q) (OR:1.298, 95% CI: 0.331-5.086,p=0.124), +21(OR:1.817, 95% CI:0.429-7698,p=0.124) and t(8;21) (OR:3.028, 95% CI: 0.604-15.172,p=0.137) groups, the difference did not reach statistical significiance. Our results do not support the view that the C609T polymorphism has a role in the pathogenesis of MDS. Also the frequency of the C609T allele did not seem to be associated with cytogenetic abnormalities.
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PMID:The frequency of C609T polymorphism in the NQO1 gene and its relation to cytogenetic abnormalities in patients with myelodysplastic syndrome. 2745 74