Influence of detection of pretreatment cytogenetic abnormalities on first complete remission and survival in adult acute lymphoblastic leukemia

Objective: Treatment of acute lymphoblastic leukemia (ALL) in adults focuses on the initial assessment of the prognostic relevant cytogenetic features as well as a response-guided therapy based on molecular data. We examined the importance of molecular-cytogenetic abnormalities for complete remission (CR) rates and the overall survival (OS) in adult ALLs.Materials and Methods: Conventional cytogenetics and fluorescence in situ hybridization were performed on bone marrow cells from 33 newly-diagnosed ALL adults. Two karyotype categories [standard- risk group- normal karyotype, hyperdiplody and other structural aberrations, and high-risk group-t(11q23)/MLL, t(9;22)/bcr-abl, t(1;19), t(8;14), C-MYC and complex karyotype] and the biologically and clinically relevant ALL ploidy subgroups were prospectively defined.Results: Chromosomal abnormalities were found in 52% of the cases with a high rate of poor-risk translocations - t(9;22), t(8q24), t(11q23), t(1;19). The total CR rate was 67% and the median time for achievement 2.33 months. Male sex, an age below 35 years and the absence of high risk translocations might have contributed to the high CR rates. Female patients, hyperdiplody, low white blood cells (WBC), and random cytogenetic aberrations had the longest OS. OS, 3- and 5-years survival periods were significantly shorter for poor-risk than standard risk group (p=.015, p=.001 and p=.005, respectively).Conclusion: This study emphasizes the lack of influence of cytogenetic aberrations on the CR and the time to achieve CR. However, our observations show that these aberrations are an independent prognostic factor in adult ALL - they allow predicting therapy resistance and the OS time after intensetreatment

Influence of detection of pretreatment cytogenetic abnormalities on first complete remission and survival in adult acute lymphoblastic leukemia Erişkin akut lenfoblastik lösemide ilk tam remisyon ve sağkalım üzerinde tedavi öncesi sitogenetik anomalilerin

Abstract Objective: Treatment of acute lymphoblastic leukemia (ALL) in adults focuses on the initial assessment of the prognostic relevant cytogenetic features as well as a response-guided therapy based on molecular data. We examined the importance of molecular-cytogenetic abnormalities for complete remission (CR) rates and the overall survival (OS) in adult ALLs. Materials and Methods: Conventional cytogenetics and fluorescence in situ hybridization were performed on bone marrow cells from 33 newly-diagnosed ALL adults. Two karyotype categories [standard-risk group-normal karyotype, hyperdiplody and other structural aberrations, and high-risk group-t(11q23)/MLL, t(9;22)/bcr-abl, t(1;19), t(8;14), C-MYC and complex karyotype] and the biologically and clinically relevant ALL ploidy subgroups were prospectively defined. Results: Chromosomal abnormalities were found in 52% of the cases with a high rate of poor-risk translocations -t(9;22), t(8q24), t(11q23), t(1;19). The total CR rate was 67% and the median time for achievement 2.33 months. Male sex, an age below 35 years and the absence of high risk translocations might have contributed to the high CR rates. Female patients, hyperdiplody, low white blood cells (WBC), and random cytogenetic aberrations had the longest OS. OS, 3-and 5-years survival periods were significantly shorter for poor-risk than standard risk group (p=.015, p=.001 and p=.005, respectively). Conclusion: This study emphasizes the lack of influence of cytogenetic aberrations on the CR and the time to achieve CR. However, our observations show that these aberrations are an independent prognostic factor in adult ALL -they allow predicting therapy resistance and the OS time after intense treatment. (Turk J Hematol 2011; 28: 176-85

Association between Helicobacter pylori infection and the presence of anti-sperm antibodies

The aim of this study was to investigate the possible association between serum anti-Helicobacter pylori antibodies and anti-sperm antibodies (ASA) in patients with gastroduodenal diseases caused by H. pylori, infertile patients positive for ASA and healthy fertile blood donors as controls. Serum ASA were studied by sperm agglutination tests, sperm immobilization test and ELISA against sperm antigens (ELISAsp). Serum IgG anti-H. pylori antibodies were detected by ELISA (ELISAHp). The tests revealed significantly higher incidence of ASA in patients with gastroduodenal diseases compared to the controls (P < 0.0001). The median levels of both types of antibodies were significantly higher in infertile patients than in patients with upper gastroduodenal diseases in all tests applied (sperm agglutination and immobilization tests P < 0.0001; ELISAsp P = 0.006; ELISAHp, P = 0.0008). Significant linear correlation was found between anti-H. pylori antibodies and ASA detected by sperm immobilization test (r = 0.613, P = 0.05) in the group of patients with gastroduodenal disease, as well as a weak linear correlation was established between anti-H. pylori antibodies and ASA in ELISAsp (r = 0.275, P = 0.0051) in the same group. These results suggest that H. pylori infection may play a role in the induction of ASA

Case-control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population

The development of molecular psychiatry in the last few decades identified a number of candidate genes that could be associated with schizophrenia. A great number of studies often result with controversial and non-conclusive outputs. However, it was determined that each of the implicated candidates would independently have a minor effect on the susceptibility to that disease. Herein we report results from our replication study for association using 255 Bulgarian patients with schizophrenia and schizoaffective disorder and 556 Bulgarian healthy controls. We have selected from the literatures 202 single nucleotide polymorphisms (SNPs) in 59 candidate genes, which previously were implicated in disease susceptibility, and we have genotyped them. Of the 183 SNPs successfully genotyped, only 1 SNP, rs6277 (C957T) in the DRD2 gene (P=0.0010, odds ratio=1.76), was considered to be significantly associated with schizophrenia after the replication study using independent sample sets. Our findings support one of the most widely considered hypotheses for schizophrenia etiology, the dopaminergic hypothesis

Whole-genome-wide association study in the Bulgarian population reveals HHAT as schizophrenia susceptibility gene [Article]

Objective: Schizophrenia, the most common major psychiatric disorder (or group of disorders), entails severe decline of higher functions, principally with alterations in cognitive functioning and reality perception. Both genetic and environmental factors are involved in its pathogenesis; however, its genetic background still needs to be clarified. The objective of the study was to reveal genetic markers associated with schizophrenia in the Bulgarian population. Methods: We have conducted a genome-wide association study using 554 496 single nucleotide polymorphisms (SNPs) in 188 affected and 376 unaffected Bulgarian individuals. Subsequently, the 100 candidate SNPs that revealed the smallest P-values were further evaluated in an additional set of 99 case and 328 control samples. Results: We found a significant association between schizophrenia and the intronic SNP rs7527939 in the HHAT gene (P-value of 6.49×10−9 with an odds ratio of 2.63, 95% confidence interval of 1.89–3.66). We also genotyped additional SNPs within a 58-kb linkage disequilibrium block surrounding the landmark SNP. Conclusion: We suggest rs7527939 to be the strongest indicator of susceptibility to schizophrenia in the Bulgarian population within the HHAT locus

Case–control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population

The development of molecular psychiatry in the last few decades identified a number of candidate genes that could be associated with schizophrenia. A great number of studies often result with controversial and non-conclusive outputs. However, it was determined that each of the implicated candidates would independently have a minor effect on the susceptibility to that disease. Herein we report results from our replication study for association using 255 Bulgarian patients with schizophrenia and schizoaffective disorder and 556 Bulgarian healthy controls. We have selected from the literatures 202 single nucleotide polymorphisms (SNPs) in 59 candidate genes, which previously were implicated in disease susceptibility, and we have genotyped them. Of the 183 SNPs successfully genotyped, only 1 SNP, rs6277 (C957T) in the DRD2 gene (P=0.0010, odds ratio=1.76), was considered to be significantly associated with schizophrenia after the replication study using independent sample sets. Our findings support one of the most widely considered hypotheses for schizophrenia etiology, the dopaminergic hypothesis

Abstracts Of The Proceedings And The Posters From The Third Scientific Session Of The Medical College Of Varna

October 2-3, 201