18 results on '"Aggeliki Daraki"'
Search Results
2. Erdheim–Chester Disease and Acute Myeloid Leukemia with Mutated NPM1 in a Patient with Clonal Hematopoiesis: A Case Report
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Thomas P. Thomopoulos, Aspasia Divane, Efthymia Bazani, Aggeliki Daraki, Andreas F. Mavrogenis, Fotini Ieremiadou, Periklis G. Foukas, Anthi Bouchla, Ioannis Panayiotides, Vasiliki Pappa, Sotirios G. Papageorgiou, Maria Roumelioti, Alexandros Georgakopoulos, Sofia Chatziioannou, Christine Kottaridi, and Panayiotis Panayiotidis
- Subjects
0301 basic medicine ,NPM1 ,Myeloid ,genetic structures ,business.industry ,Myeloid leukemia ,medicine.disease ,Acute Myeloid Leukemia with Mutated NPM1 ,03 medical and health sciences ,chemistry.chemical_compound ,Histiocytosis ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Erdheim–Chester disease ,Cancer research ,medicine ,Neoplasm ,Pharmacology (medical) ,Midostaurin ,business - Abstract
Background Erdheim-Chester Disease (ECD) is a clonal non-Langerhans histiocytosis, classified as a macrophage-dendritic cell neoplasm in the 2016 WHO classification. The exact cell of origin of ECD is unknown, although some limited evidence suggests that it arises from myeloid progenitors. Case presentation A 43-year-old patient, diagnosed with BRAF V600E mutated ECD, developed NPM1+/FLT3+ acute myeloid leukemia (AML) with wild-type BRAF, 15 months after the initial ECD diagnosis. The patient received intensive chemotherapy plus midostaurin, followed by midostaurin maintenance. Six months into maintenance, the patient remains in complete remission with low-level measurable residual disease, whereas ECD shows a sustained partial metabolic response. Molecular karyotype at several distinct timepoints, namely ECD diagnosis, AML diagnosis, and following treatment of AML, highlighted a molecular signature, indicative of a persistent, underlying clonal hematopoiesis. Conclusion This case report suggests that ECD and AML might represent an expansion of two distinct clones in a background of clonal hematopoiesis, indicating their shared origin. Moreover, molecular karyotype might serve as a strong, inexpensive tool for revealing clonal hematopoiesis in cases of negative targeted next-generation sequencing. Finally, the moderate response of ECD to midostaurin suggests that kinase inhibition might have a potential role in ECD treatment.
- Published
- 2020
3. Κυτταρογενετική και μοριακή μελέτη ασθενών με πρωτοπαθή και δευτεροπαθή οξεία μυελογενή λευχαιμία
- Author
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Aggeliki Daraki
- Abstract
Η Οξεία Μυελογενής Λευχαιμία (ΟΜΛ) αποτελεί μια νόσο με μεγάλη ετερογένεια. Η αιτιολογία ανάπτυξης της νόσου δεν έχει πλήρως αποσαφηνιστεί, ωστόσο στην πολυσταδιακή πορεία της, φαίνεται να εμπλέκονται γενετικοί, επιγενετικοί και περιβαλλοντικοί παράγοντες. Σκοπός της παρούσας διδακτορικής διατριβής ήταν η διερεύνηση του ρόλου των πολυμορφισμών των γονιδίων αποτοξικοποίησης CYP2B6 (G516T, C777A, A785G), GSTP1 (A313G) και των γονιδίων επιδιόρθωσης RAD51 (G135C), XPD23 (Α23927C) και LIG4 (C26T) στην προδιάθεση εμφάνισης της ΟΜΛ. Επίσης, μελετήθηκε η συσχέτιση της μεθυλίωσης του υποκινητή του γονιδίου GSTP1 και ανάπτυξη της ΟΜΛ. Αναλύθηκαν 619 ασθενείς με ΟΜΛ και 430 υγιείς δότες. Η μεθοδολογία που ακολουθήθηκε περιλαμβάνει την κυτταρογενετική ανάλυση δειγμάτων μυελού των οστών ασθενών, τη γονοτυπική ανάλυση των προαναφερθέντων πολυμορφισμών και τον έλεγχο μεθυλίωσης του υποκινητή του γονιδίου GSTP1. Τα αποτελέσματα της παρούσας έρευνας ανέδειξαν τον πιθανό ρόλο των πολυμορφισμών G516T και A785G του γονιδίου CYP2B6 καθώς και των πολυμορφισμών A313G και C26T των γονιδίων GSTP1 και LIG4, αντίστοιχα, στην προδιάθεση ανάπτυξης ΟΜΛ. Αντιθέτως, ο πολυμορφισμός C777A του γονιδίου CYP2B6 καθώς και οι πολυμορφισμοί G135C, Α23927C των γονιδίων επιδιόρθωσης RAD51 και XPD23, αντιστοιχα, παρουσίασαν παρόμοια κατανομή συχνοτήτων μεταξύ ασθενών και μαρτύρων, γεγονός που υποδηλώνει ότι πιθανότατα η παρουσία των πολυμορφισμών αυτών δεν αυξάνουν τον κίνδυνο ανάπτυξης ΟΜΛ. Για το γονίδιο CYP2B6 πραγματοποιήθηκε και η δημιουργία των απλοτύπων για τους υπό μελέτη πολυμορφισμούς. Ενδιαφέρον παρουσιάζει το γεγονός τα άτομα που έφεραν τον απλότυπο TAG (συνύπαρξη των τριών μεταλλαγμένων γονοτύπων) έχουν 3-φορές μεγαλύτερη πιθανότητα ανάπτυξης της νόσου σε σύγκριση με τους μάρτυρες. Από τις μελέτες συσχετίσεων μεταξύ των γονοτύπων των υπό μελέτη γονιδίων με τα κυτταρογενετικά ευρήματα των ασθενών βρέθηκαν στατιστικά σημαντικές διαφορές υποδηλώνοντας έτσι το σημαντικό ρόλο των πολυμορφισμών στη δημιουργία ειδικών για την ΟΜΛ χρωμοσωμικών αλλοιώσεων. Επιπλέον, βρέθηκε ότι η μεθυλίωση του υποκινητή του γονιδίου GSTP1 απαντάται συχνότερα στους ασθενείς με δευτεροπαθή ΟΜΛ. Σύμφωνα λοιπόν με όλα τα παραπάνω, τα αποτελέσματα της παρούσας διδακτορικής διατριβής, μεμονωμένα ή συνδυαστικά, αναμένεται να συμβάλλουν στην κατανόηση του ρόλου των πολυμορφισμών γονιδίων αποτοξικοποίησης και επιδιόρθωσης στην προδιάθεση ανάπτυξης ΟΜΛ, στην εμφάνιση συγκεκριμένων κυτταρογενετικών αλλοιώσεων καθώς και στη σχεδίαση κατάλληλων εξατομικευμένων θεραπευτικών πρωτοκόλλων ανάλογα με το γενετικό υπόβαθρο των ασθενών.
- Published
- 2021
4. Paraoxonase 1 (PON1) Q192R and L55M Polymorphisms as Potential Predisposition Factors for Chronic Lymphocytic Leukemia
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Paraskevi Diamantopoulou, Domna Pantelia, Aggeliki Daraki, Kalliopi N. Manola, Sophia Zachaki, Ioanna Maria Margariti, Paraskevi Roussou, Constantina Sambani, and Agapi Ioannidou
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Adult ,Male ,Cancer Research ,Genotyping Techniques ,Chronic lymphocytic leukemia ,Biology ,Polymorphism, Single Nucleotide ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Genotype ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,In Situ Hybridization, Fluorescence ,Aged ,Aged, 80 and over ,Chromosome Aberrations ,Chromosomes, Human, Pair 14 ,medicine.diagnostic_test ,Aryldialkylphosphatase ,Paraoxonase ,General Medicine ,Middle Aged ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,PON1 ,SNP genotyping ,Oncology ,Case-Control Studies ,Karyotyping ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Chromosomes, Human, Pair 6 ,Female ,Fluorescence in situ hybridization - Abstract
Background/aim PON1 gene has an executive role in antioxidant defense, protecting cells from genotoxic factors. Q192R and L55M PON1 polymorphisms reduce catalytic activity of the encoded protein. These polymorphisms were studied in 300 chronic lymphocytic leukemia (CLL) patients and 106 healthy donors. They were also associated with patients' cytogenetic findings, to investigate their possible implication in CLL pathogenesis. Materials and methods SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Karyotypic analysis was also performed by chromosome G-banding analysis and fluorescence in situ hybridization. Results Genotypic and allelic distribution of Q192R polymorphism showed a statistically significant higher frequency of mutant genotypes and mutant alleles in patients compared to controls. The same observation was noted in patients with abnormal karyotypes and those carrying abn14q32 and del(6q). A statistically increased frequency for the mutant allele was also revealed in patients with del(11q). On the contrary, L55M polymorphism showed a similar distribution between patients and controls. Conclusion Q192R polymorphism plays a role in CLL predisposition and the formation of specific chromosomal aberrations.
- Published
- 2019
5. ASXL1mutations in AML are associated with specific clinical and cytogenetic characteristics
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Aggeliki Daraki, Fotios Panitsas, Chara Giatra, Ioanna Vlachadami, Agapi Ioannidou, Maria Pagoni, Theodoros Marinakis, Kalliopi N. Manola, Diamantina Vasilatou, Katerina Kakosaiou, Constantina Sambani, Paraskevi Apostolou, and Vassiliki Pappa
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Adult ,Male ,0301 basic medicine ,Cancer Research ,Adolescent ,Carcinogenesis ,Leukocytosis ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Humans ,Medicine ,Aged ,Chromosome Aberrations ,business.industry ,Age Factors ,Myeloid leukemia ,Neoplasms, Second Primary ,Hematology ,Middle Aged ,Repressor Proteins ,Leukemia, Myeloid, Acute ,030104 developmental biology ,Oncology ,Case-Control Studies ,Myelodysplastic Syndromes ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,Female ,business - Abstract
Mutations of ASXL1 are early events in acute myeloid leukemia (AML) leukemogenesis and have been associated with unfavorable prognosis. In this study, we investigated the type and frequency of ASXL1 mutations in a large cohort of patients with de novo or secondary AML (s-AML) and looked for correlations with cytogenetic findings and disease features. ASXL1 mutations were associated with older age, s-AML and higher peripheral leukocytosis. We observed more frequent co-occurrence of ASXL1 mutations with trisomy 8 and chromosome 11 aberrations but a negative correlation with myelodysplastic syndromes (MDS)-related cytogenetic abnormalities, especially -5/del(5q) and -7/del(7q). ASXL1 mutations were also found in other genetically defined AML subgroups such as those with t(9;22), inv(3)/t(3;3), t(8;21) or t(15;17); however, none of our inv(16) cases carried ASXL1 mutations. We detected two previously unreported ASXL1 mutations, p.IIe593Val and p.Cys688Tyr. Our findings suggest that ASXL1 mutations tend to cluster with specific clinical and cytogenetic profiles of AML patients.
- Published
- 2018
6. Cohesin RAD21 Gene Promoter Methylation in Patients with Chronic Lymphocytic Leukemia
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Aggeliki Daraki, Maria Karakosta, Sophia Zachaki, Kalliopi N. Manola, Agapi Ioannidou, and Paraskevi Roussou
- Subjects
0301 basic medicine ,Chronic lymphocytic leukemia ,Promoter ,Methylation ,Biology ,medicine.disease ,03 medical and health sciences ,Leukemia ,030104 developmental biology ,CpG site ,immune system diseases ,hemic and lymphatic diseases ,DNA methylation ,Genetics ,Cancer research ,medicine ,Epigenetics ,neoplasms ,Molecular Biology ,Gene ,Genetics (clinical) - Abstract
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults and is characterized by the presence of specific cytogenetic abnormalities. CLL research has been focused on epigenetic processes like gene promoter methylation of CpG islands. In the present study, the methylation status of the RAD21 gene is studied and associated with cytogenetic findings in CLL patients in order to investigate its possible implication in CLL pathogenesis and the formation of CLL chromosomal abnormalities.
- Published
- 2018
7. Association of C609T-Inborn Polymorphism of NAD(P)H: Quinone Oxidoreductase 1 with the Risk of Bronchopulmonary Dysplasia in Preterm Neonates
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Chryssa Stavropoulou, George Baroutis, Kalliopi N. Manola, Aggeliki Daraki, Elena Polycarpou, Sophia Zachaki, Stavroula Gavrili, and Constantina Sambani
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Male ,medicine.medical_specialty ,Pathology ,Birth weight ,Mutant ,Single-nucleotide polymorphism ,medicine.disease_cause ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,behavioral disciplines and activities ,Gene Frequency ,Internal medicine ,mental disorders ,NAD(P)H Dehydrogenase (Quinone) ,Humans ,Medicine ,Genetic Predisposition to Disease ,Genotyping ,Alleles ,Bronchopulmonary Dysplasia ,Greece ,business.industry ,Infant, Newborn ,Obstetrics and Gynecology ,Gestational age ,medicine.disease ,Logistic Models ,Endocrinology ,Bronchopulmonary dysplasia ,Case-Control Studies ,Pediatrics, Perinatology and Child Health ,Female ,Gene polymorphism ,business ,Infant, Premature ,Oxidative stress - Abstract
Objectives In bronchopulmonary dysplasia (BPD), direct exposure to oxygen therapy can damage the pulmonary epithelium via oxidative stress. The NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme detoxifies genotoxic products of oxidative stress. The corresponding gene is subject to an inactivating single-nucleotide polymorphism (C 609 T), which reduces detoxifying ability. The aim of this study was to investigate whether the C 609 T NQO1 inborn gene polymorphism is associated with an increased risk of BPD. Study Design Peripheral blood samples from 119 premature neonates ≤ 32 weeks of gestational age (42 BPD and 77 non-BPD) were used for DNA extraction. NQO1 genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. Results A significantly higher frequency of the NQO1 polymorphism was observed in BPD neonates compared with neonates without BPD. All neonates with ≤ 1,000 g birth weight who carried the mutant allele in heterozygous or homozygous state developed BPD. None of the BPD nonaffected group neonates with ≤ 1,000 g birth weight carried the NQO1 polymorphism. Conclusion The higher incidence of NQO1 mutants among BPD neonates as well as the presence of the mutant allele in all neonates with ≤ 1,000 g who developed BPD provided the first evidence for a possible pathogenetic role of the C 609 T polymorphism in BPD susceptibility due to the reduction or loss of NQO1 enzymatic activity.
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- 2015
8. Association of GSTP1 inactivating polymorphism with acute myeloid leukemia and its specific chromosomal abnormalities
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Marina Kalomoiraki, Panagoula Kollia, Kalliopi N. Manola, Vassiliki Aleporou-Marinou, Sophia Zachaki, Aggeliki Daraki, Faidra Rosmaraki, and Constantina Sambani
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Male ,0301 basic medicine ,Cancer Research ,Myeloid ,genetic structures ,Disease ,03 medical and health sciences ,GSTP1 ,0302 clinical medicine ,hemic and lymphatic diseases ,Biomarkers, Tumor ,medicine ,Humans ,neoplasms ,Chromosome Aberrations ,Acute leukemia ,Polymorphism, Genetic ,Genetic heterogeneity ,business.industry ,Case-control study ,Myeloid leukemia ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,eye diseases ,Leukemia, Myeloid, Acute ,Leukemia ,030104 developmental biology ,medicine.anatomical_structure ,Glutathione S-Transferase pi ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Cancer research ,Female ,sense organs ,business ,Follow-Up Studies - Abstract
Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease and the most common acute leukemia in adults. Many genotoxic factors have been accused for AML development but onl...
- Published
- 2017
9. Cohesin RAD21 Gene Promoter Methylation in Patients with Chronic Lymphocytic Leukemia
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Agapi, Ioannidou, Sophia, Zachaki, Maria, Karakosta, Aggeliki, Daraki, Paraskevi, Roussou, and Kalliopi N, Manola
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Adult ,Aged, 80 and over ,Male ,Nuclear Proteins ,Cell Cycle Proteins ,DNA Methylation ,Middle Aged ,Phosphoproteins ,Leukemia, Lymphocytic, Chronic, B-Cell ,DNA-Binding Proteins ,Cytogenetic Analysis ,Humans ,Female ,Promoter Regions, Genetic ,Aged - Abstract
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults and is characterized by the presence of specific cytogenetic abnormalities. CLL research has been focused on epigenetic processes like gene promoter methylation of CpG islands. In the present study, the methylation status of the RAD21 gene is studied and associated with cytogenetic findings in CLL patients in order to investigate its possible implication in CLL pathogenesis and the formation of CLL chromosomal abnormalities.
- Published
- 2018
10. GSTP1 and CYP2B6 Genetic Polymorphisms and the Risk of Bronchopulmonary Dysplasia in Preterm Neonates
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Elena Polycarpou, Kalliopi N. Manola, Aggeliki Daraki, Sophia Zachaki, Stavroula Gavrili, and Chrysa Stavropoulou
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0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Single-nucleotide polymorphism ,Gestational Age ,urologic and male genital diseases ,behavioral disciplines and activities ,Polymorphism, Single Nucleotide ,Pathogenesis ,03 medical and health sciences ,GSTP1 ,0302 clinical medicine ,mental disorders ,Genotype ,medicine ,Humans ,Infant, Very Low Birth Weight ,Genetic Predisposition to Disease ,030212 general & internal medicine ,Genotyping ,Bronchopulmonary Dysplasia ,Greece ,business.industry ,Infant, Newborn ,Obstetrics and Gynecology ,Gestational age ,medicine.disease ,Low birth weight ,Cytochrome P-450 CYP2B6 ,Oxidative Stress ,030104 developmental biology ,Bronchopulmonary dysplasia ,Glutathione S-Transferase pi ,Case-Control Studies ,Pediatrics, Perinatology and Child Health ,Immunology ,Female ,medicine.symptom ,business ,Infant, Premature - Abstract
Objectives Antioxidant response plays a key role in bronchopulmonary dysplasia (BPD) pathogenesis. The glutathione-S-tranferases pi 1 (GSTP1) and cytochrome P450 (CYP) detoxification enzymes protect cells from oxidative damage. The aim of the study was to investigate whether the A313G GSTP1 and G516T CYP2B6 inactivating polymorphisms could be associated with BPD susceptibility. Study Design To test this hypothesis, we conducted a case–control study enrolled 138 premature neonates ≤32 weeks of gestational age; of the 138, 46 developed BPD and 92 did not develop BPD. Genomic deoxyribonucleic acid was extracted from neonates' peripheral blood and was used as template for GSTP1 and CYP2B6 genotyping using the real-time polymerase chain reaction method. Results Our report provides evidence for a possible pathogenetic role of the G516T CYP2B6 polymorphism in BPD susceptibility. Although no differences in the frequencies of the GSTP1 variant genotypes were noticed between premature neonates who developed BPD and neonates who did not develop BPD, a significantly higher frequency of the GSTP1 polymorphism was observed in extremely low birth weight infants. Despite the small sample size, it is very interesting the fact that all neonates ≤1,000 g carrying the homozygous mutant GSTP1 genotype developed BPD. Conclusion Our results underscore the significance of both CYP2B6 and GSTP1 polymorphisms in modulating the risk of BPD.
- Published
- 2017
11. High frequency of NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T germline polymorphism in MDS/AML with trisomy 8
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Chrysa Stavropoulou, Constantina Sambani, Emmanuel Kanavakis, Sophia Zachaki, Kalliopi N. Manola, Theodora Koromila, Daphne Koumbi, Aggeliki Daraki, Marina Kalomoiraki, Anastasia Athanasiadou, and Panagoula Kollia
- Subjects
Adult ,Male ,Cancer Research ,Myeloid ,Genotype ,Trisomy ,Biology ,Trisomy 8 ,Polymerase Chain Reaction ,Germline ,Young Adult ,hemic and lymphatic diseases ,NAD(P)H Dehydrogenase (Quinone) ,medicine ,Genetic predisposition ,Humans ,Genotyping ,Germ-Line Mutation ,Aged ,Retrospective Studies ,Aged, 80 and over ,Chromosome Aberrations ,Polymorphism, Genetic ,Case-control study ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Molecular biology ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,Oncology ,Case-Control Studies ,Myelodysplastic Syndromes ,Female ,Polymorphism, Restriction Fragment Length ,Chromosomes, Human, Pair 8 ,Follow-Up Studies - Abstract
The NQO1 C(609)T germline polymorphism resulting in a lowering of enzyme activity may confer susceptibility to MDS. To assess this association, we performed a case-control study including 330 Greek patients with de novo MDS and 416 healthy donors, using a Real-Time PCR genotyping method. Focusing on cytogenetic aberrations most commonly found in MDS, we retrospectively genotyped 566 MDS/AML patients carrying -5/del(5q), -7/del(7q), +8, del(20q) and -Y. The case-control analysis revealed no differences in NQO1 genotype distribution. Interestingly, a 6-fold increased frequency of the homozygous variant genotype was observed among patients with isolated trisomy 8 (p
- Published
- 2013
12. Association of A313G glutathione S-transferase P1 germline polymorphism with susceptibility tode novomyelodysplastic syndrome
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Gabriel E. Pantelias, Aggeliki Daraki, Kalliopi N. Manola, Emmanuel Kanavakis, Ariadni Mavrou, Sophia Zachaki, Marina Kalomoiraki, Theodora Koromila, Chrysa Stavropoulou, and Constantina Sambani
- Subjects
Adult ,Male ,Cancer Research ,Adolescent ,Genotype ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Young Adult ,GSTP1 ,Gene Frequency ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,Genotyping ,Alleles ,Germ-Line Mutation ,Aged ,Aged, 80 and over ,Chromosome Aberrations ,Genetics ,De novo Myelodysplastic Syndrome ,Heterozygote advantage ,Hematology ,Middle Aged ,Molecular biology ,Glutathione S-transferase ,Amino Acid Substitution ,Glutathione S-Transferase pi ,Oncology ,Case-Control Studies ,Myelodysplastic Syndromes ,biology.protein ,Female - Abstract
Models for the pathogenesis of myelodysplastic syndrome (MDS) imply the role of individual genetic variations in genes involved in detoxification mechanisms. GSTP1 enzyme plays a key role in the biotransformation of a variety of carcinogens. The corresponding gene is subject to a single nucleotide polymorphism (A(313)G) leading to abolished enzyme activity. In order to evaluate whether the GSTP1 polymorphism influences MDS susceptibility, we conducted a case-control study comprising 310 de novo patients and 370 healthy controls using a real-time polymerase chain reaction (PCR) genotyping method. The GSTP1 gene status was also evaluated in relation to patients' characteristics and chromosomal abnormalities. A significantly higher incidence of the GSTP1 variant genotypes was observed in patients with MDS compared to controls (p0.0001). The results revealed increased frequencies of heterozygotes in patients younger than 60 years old and of homozygotes G/G in older patients (p = 0.007). Our results provide evidence for a pathogenetic role of the GSTP1 polymorphism in MDS risk, probably in an age-dependent manner.
- Published
- 2013
13. Polymorphisms and haplotypes of the CYP2B6 detoxification gene in the predisposition of Acute Myeloid Leukemia (AML) and induction of its cytogenetic abnormalities
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Vassiliki Aleporou-Marinou, Katerina Kakosaiou, Aggeliki Daraki, Sophia Zachaki, Panagoula Kollia, Constantina Sambani, and Kalliopi N. Manola
- Subjects
0301 basic medicine ,Male ,Cancer Research ,medicine.medical_specialty ,CYP2B6 ,Genotyping Techniques ,Mutant ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Genotype ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Molecular Biology ,Gene ,Chromosome Aberrations ,Haplotype ,Cytogenetics ,Myeloid leukemia ,Cytochrome P-450 CYP2B6 ,Leukemia, Myeloid, Acute ,030104 developmental biology ,Haplotypes ,030220 oncology & carcinogenesis ,Cytogenetic Analysis ,Female - Abstract
CYP2B6 is a polymorphic detoxification gene which plays a vital role in the degradation of genotoxic compounds. In this study we hypothesized that inadequate detoxification due to CYP2B6 polymorphisms may contribute to AML. To evaluate the potential impact of CYP2B6 polymorphisms on AML development and induction of its specific chromosomal abnormalities we studied C 777 A and A 785 G polymorphisms for the first time in AML. Furthermore, we investigated the co-existence of the above polymorphisms with G 516 T polymorphism to determine the CYP2B6 high-risk haplotypes in AML susceptibility. Our study included 619 AML patients and 430 healthy donors. Concerning C 777 A CYP2B6 polymorphism, no significant difference was found between patients and controls. However, A 785 G CYP2B6 polymorphism showed a statistically higher frequency of the variant genotypes in patients (48.2%), mainly in secondary AML patients (49.1%) than in controls (26.1%). Moreover, an increased frequency of the variant genotypes was found in those with abnormal karyotypes, especially with −7/del(7q), −5/del(5q), +8, inv(16) and t(8;21). The combination of the three CYP2B6 polymorphisms (G 516 T, C 777 A & A 785 G) revealed seven haplotypes. Four out of six haplotypes with at least one mutant allele were significantly associated with an increased risk for AML. Interestingly, T 516 A 777 G 785 haplotype, where the three mutant alleles co-existed, had ~3-fold increased risk to be found in patients than controls. The association between haplotypes and cytogenetic aberrations revealed a positive correlation between specific CYP2B6 haplotypes and AML cytogenetic abnormalities. Our data suggest that A 785 G CYP2B6 gene polymorphism and specific CYP2B6 haplotypes may contribute to AML and its specific chromosomal aberrations.
- Published
- 2016
14. Glutathione S-transferase P1 promoter hypermethylation in acute myeloid leukemia: association with A313G germline polymorphism and chromosomal abnormalities
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Sophia Zachaki, Kalliopi N. Manola, Constantina Sambani, Aggeliki Daraki, Chrysa Stavropoulou, and Vassiliki Aleporou-Marinou
- Subjects
Cancer Research ,Myeloid ,biology ,Myeloid leukemia ,Hematology ,medicine.disease ,Germline ,Leukemia ,Haematopoiesis ,medicine.anatomical_structure ,Germline mutation ,Glutathione S-transferase ,Oncology ,hemic and lymphatic diseases ,medicine ,Cancer research ,biology.protein ,Bone marrow - Abstract
Acute myeloid leukemia (AML) is defined as a clonal proliferation of immature hematopoietic progenitors with varying degree of myeloid differentiation in the bone marrow, peripheral blood or extram...
- Published
- 2014
15. Cytogenetic abnormalities and monosomal karyotypes in children and adolescents with acute myeloid leukemia: correlations with clinical characteristics and outcome
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Aggeliki Daraki, Constantina Sambani, Cryssa Stavropoulou, Georgia Avgerinou, Emmanuel Hatzipantelis, Maria Pagoni, Kalliopi N. Manola, Fotios Panitsas, Maria Karakosta, Gabriel E. Pantelias, and Sophia Polychronopoulou
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Karyotype ,Kaplan-Meier Estimate ,Biology ,Leukemia, Myelomonocytic, Acute ,Translocation, Genetic ,Cohort Studies ,Young Adult ,Monosomy ,Leukemia, Promyelocytic, Acute ,Leukemia, Megakaryoblastic, Acute ,Cytogenetic Abnormality ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Genetics ,medicine ,Humans ,Child ,Molecular Biology ,Chromosome 7 (human) ,Chromosome Aberrations ,Incidence (epidemiology) ,Cytogenetics ,Myeloid leukemia ,Infant ,Prognosis ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Leukemia, Myeloid ,Child, Preschool ,Karyotyping ,Cohort ,Acute Disease ,Leukemia, Monocytic, Acute ,Leukemia, Erythroblastic, Acute - Abstract
The whole spectrum of chromosomal abnormalities and their prognostic significance in children and adolescents with acute myeloid leukemia (AML) has not been fully elucidated yet, although a considerable amount of knowledge has been gained recently. Moreover, the incidence and prognostic impact of monosomal karyotypes (MKs), which are new cytogenetic categories reported recently in adults with AML, are currently unknown for childhood and adolescent AML. In this study, we investigated the cytogenetic and clinical characteristics of 140 children and adolescents (≤21 y) with AML, and correlated their cytogenetic features with both the clinical characteristics and outcomes of our patient cohort. The most frequent cytogenetic abnormality found in our study was the t(15;17), followed by the t(8;21). Striking differences in the genetic abnormalities and French-American-British subtypes were found among infants, children, and adolescents. Of 124 cases, 15 (12.1%) met the criteria of the MK definition, and 12 of the 15 MKs (80%) were complex karyotypes. Of 124 cases, 27 (21.8%) had cytogenetic abnormalities sufficient to be diagnosed as AML with myelodyspastic sydrome–related features. As expected, patients with the t(15;17) had the most favorable outcomes, whereas patients with 11q23 rearrangements and monosomy 7 had the worst outcomes. These data expand our knowledge by providing novel insights into the cytogenetic features and their correlations with clinical characteristics and outcomes in childhood and adolescent AML.
- Published
- 2012
16. The G516T CYP2B6 Germline Polymorphism Affects the Risk of Acute Myeloid Leukemia and Is Associated with Specific Chromosomal Abnormalities
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Gabriel E. Pantelias, Theodora Koromila, Vasiliki Aleporou, Sophia Zachaki, Constantina Sambani, Aggeliki Daraki, Panagoula Kollia, Kalliopi N. Manola, and Paraskevi Diamantopoulou
- Subjects
Candidate gene ,Heredity ,Myeloid ,Chromosome Disorders ,Hematologic Cancers and Related Disorders ,Loss of heterozygosity ,0302 clinical medicine ,Molecular Cell Biology ,Genotype ,0303 health sciences ,Multidisciplinary ,Chromosome Biology ,Myeloid leukemia ,3. Good health ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cytogenetic Analysis ,Medicine ,Research Article ,Acute Myeloid Leukemia ,Risk ,Chromosome Structure and Function ,Clinical Research Design ,Genotypes ,Karyotype ,Biology ,Molecular Genetics ,Cytogenetics ,03 medical and health sciences ,Genetic Mutation ,Leukemias ,Genetics ,Cancer Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Genotyping ,Genetic Association Studies ,Alleles ,Germ-Line Mutation ,030304 developmental biology ,Chromosome Aberrations ,Polymorphism, Genetic ,Mutation Types ,Cancers and Neoplasms ,Human Genetics ,medicine.disease ,Molecular biology ,Cytochrome P-450 CYP2B6 ,Case-Control Studies ,Karyotyping ,Genetic Polymorphism ,Population Genetics - Abstract
The etiology of acute myeloid leukemia (AML) underlies the influence of genetic variants in candidate genes. The CYP2B6 enzyme detoxifies many genotoxic xenobiotics, protecting cells from oxidative damage. The CYP2B6 gene is subjected to a single-nucleotide polymorphism (G516T) with heterozygotes (GT) and homozygotes (TT) presenting decreased enzymatic activity. This case-control study aimed to investigate the association of CYP2B6 G516T polymorphism with the susceptibility of AML and its cytogenetic and clinical characteristics. Genotyping was performed on 619 AML patients and 430 healthy individuals using RCR-RFLP and a novel LightSNip assay. The major finding was a statistically higher frequency of the variant genotypes (GT and TT) in patients compared to the controls (GT:38.8% vs 29.8% and TT:9.3% vs 5.3% respectively) (p
- Published
- 2014
17. Association of A313g Glutathione S-Transferase P1 (GSTP1) Inborn Polymorphism with Susceptibility to De Novo MDS
- Author
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Sophia Zachaki, Vassiliki Aleporou, Gabriel E. Pantelias, Marina Kalomoiraki, Chryssa Stavropoulou, Emmanuel Kanavakis, Panagoula Kollia, Constantina Sambani, and Aggeliki Daraki
- Subjects
Genetics ,Immunology ,Heterozygote advantage ,Single-nucleotide polymorphism ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,Molecular biology ,GSTP1 ,Genotype ,Chromosome abnormality ,medicine ,Allele ,Genotyping ,Allele frequency - Abstract
Abstract 1445 Models for the pathogenesis of myelodysplastic syndromes (MDS) imply the role of individual genetic variations in genes involved in detoxification mechanisms. GSTP1 enzyme plays a key role in detoxification of a variety of electrophilic compounds, such as benzo [a]-pyrene and other polycyclic aromatic hydrocarbons (PAHs), chemotherapy drugs and products of oxidative stress. GSTP1 acts through a common mechanism of conjugating reactive oxygen species (ROS) with glutathione, enabling their detoxification and elimination and thus defending tissues against DNA damage. The corresponding gene is subject to a single-nucleotide polymorphism (A313G) leading to abolished enzyme activity. Thus, individuals homozygous for the variant G allele (G/G) have a lower conjugating activity than individuals homozygous for the wild type A allele (A/A), while heterozygotes (A/G) display intermediate activity. The aim of the present study was to evaluate whether the GSTP1 polymorphism influences susceptibility to MDS and/or promote specific chromosomal aberrations. We conducted a case-control study in 310 de novo MDS patients and 370 unrelated healthy controls using both a conventional PCR-RFLP assay and a novel Real-Time PCR genotyping method using hybridization probe technology. The GSTP1 gene status was also evaluated in relation to patients' characteristics and chromosomal abnormalities. Comparison of the genotype distribution between controls and MDS cases revealed a significantly higher frequency of the variant genotypes (heterozygotes A/A and homozygotes G/G) among MDS patients, as compared to controls (p Disclosures: No relevant conflicts of interest to declare.
- Published
- 2012
18. the G516 Polymorphism of Cytochrome P450 2B6 Gene in the Susceptibility of De Novo Acute Myeloid Leukemia
- Author
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Kalliopi N. Manola, Gabriel E. Pantelias, Maria Karakosta, Constantina Sambani, Vasiliki Aleporou, Sophia Zachaki, Theodora Koromila, Panagoula Kollia, and Aggeliki Daraki
- Subjects
Immunology ,Wild type ,Myeloid leukemia ,Single-nucleotide polymorphism ,Heterozygote advantage ,Cell Biology ,Hematology ,Gene mutation ,Biology ,medicine.disease ,Biochemistry ,Molecular biology ,Leukemia ,Chromosome instability ,Genotype ,medicine - Abstract
Abstract 2513 Acute myeloid leukemia (AML) is a heterogeneous disease with well-known clinical and pathological aspects, characterized by the acquisition of somatic mutations in haematopoietic progenitors leading to disruption of differentiation. However, the genetic etiology of AML, which include gene mutations and chromosomal aberrations, is largely unknown. Altered forms of genes that differ by a single nucleotide polymorphisms (SNPs) have been shown to predispose individuals to AML development. Recently it has been reported that interindividual differences based on detoxification genes polymorphisms may contribute to the AML susceptibility. Human cytochrome P450 (CYP) enzymes play a key role as phase I enzymes in the metabolism of drugs and environmental chemicals. Several CYP enzymes metabolically activate procarcinogens to genotoxic intermediates. CYP2B6 blocks the transformation of precarcinogens to their biologically active forms that provoke chromosomal instability and leukemia. CYP2B6 G516T SNP change the aminoacid sequence (Gln172His), resulting in enzymatic inactivation. Thus, individuals homozygous for the mutant allele (T/T) or heterozygotes (G/T) present decreased enzymatic activity. We performed a case-control study in a large series of AML patients to investigate the potential relation between genotype of CYP2B6 G516T SNP and the risk of de novo AML. We also compared the genotypic frequencies in AML patients in respect to chromosome abnormalities, FAB classification and clinical characteristics. The CYP2B6 G516T genotyping was performed on 195 de novo AML patients at diagnosis and 215 sex and age matched healthy controls using a PCR-RFLP assay and LightSNP assay. Unstimulated bone marrow cells were used for karyotypic analysis and karyotypes were described according to ISCN. Statistical analysis was performed using Chi-square test and P Karyotypic analysis was successfully performed in 97.8% of AML patients at diagnosis. Among them, 136 (69.7%) showed clonal karyotypic abnormalities. The genotypic distribution in patients and healthy groups was statistically significant and showed: homozygous wild type G/G 54,5% vs 67.2%, heterozygotes G/T 40.4% vs 27.5% and homozygous mutant T/T 6.7% vs 5.5% respectively (p The increased frequency of mutant allele leading to reduced enzyme activity suggests that the CYP2B6 gene may be a predisposing factor for the development of AML. Furthermore, the CYP2B6 G516T polymorphism seems to be associated with the presence of lesions on chromosomes 5 and / or 7 which are poor prognostic lesions in AML. Therefore, the high frequency of mutant genotypes (G/T and T/T) of CYP2B6 G516T SNP in these cytogenetic groups may be involved in the development of these specific chromosomal abnormalities. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2012
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