Pharmacogenomic markers of glucocorticoid response in the initial phase of remission induction therapy in childhood acute lymphoblastic leukemia
| العنوان: | Pharmacogenomic markers of glucocorticoid response in the initial phase of remission induction therapy in childhood acute lymphoblastic leukemia |
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| المؤلفون: | Vita Dolzan, Sonja Pavlovic, Lidija Dokmanovic, Vladimir Gasic, Janez Jazbec, Branka Zukic, Jelena Lazic, Nikola Kotur, Nada Krstovski, Dragana Janic, Biljana Stankovic |
| المصدر: | Radiology and Oncology, Vol 52, Iss 3, Pp 296-306 (2018) Radiology and Oncology |
| بيانات النشر: | Walter de Gruyter GmbH, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Genotype, R895-920, multidrug resistance 1 gene, Blast Count, Polymerase Chain Reaction, Risk Assessment, Medical physics. Medical radiology. Nuclear medicine, 03 medical and health sciences, GSTP1, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, glucocorticoid receptor gene, Remission Induction Therapy, Biomarkers, Tumor, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Allele, Child, Childhood Acute Lymphoblastic Leukemia, pharmacogenomics, glucocorticoids, business.industry, Remission Induction, Haplotype, Genetic Variation, DNA, Neoplasm, Induction Chemotherapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, 3. Good health, Treatment Outcome, childhood all, 030104 developmental biology, Child, Preschool, 030220 oncology & carcinogenesis, Biomarker (medicine), Female, glutathione s-transferase genes, business, Research Article |
| الوصف: | Background Response to glucocorticoid (GC) monotherapy in the initial phase of remission induction treatment in childhood acute lymphoblastic leukemia (ALL) represents important biomarker of prognosis and outcome. We aimed to study variants in several pharmacogenes (NR3C1, GSTs and ABCB1) that could contribute to improvement of GC response through personalization of GC therapy. Methods Retrospective study enrolling 122 ALL patients was carried out to analyze variants of NR3C1 (rs33389, rs33388 and rs6198), GSTT1 (null genotype), GSTM1 (null genotype), GSTP1 (rs1695 and rs1138272) and ABCB1 (rs1128503, rs2032582 and rs1045642) genes using PCR-based methodology. The marker of GC response was blast count per microliter of peripheral blood on treatment day 8. We carried out analysis in which cut-off value for GC response was 1000 (according to Berlin-Frankfurt-Munster [BFM] protocol), as well as 100 or 0 blasts per microliter. Results Carriers of rare NR3C1 rs6198 GG genotype were more likely to have blast count over 1000, than the non-carriers (p = 0.030). NR3C1 CAA (rs33389-rs33388-rs6198) haplotype was associated with blast number below 1000 (p = 0.030). GSTP1 GC haplotype carriers were more likely to have blast number below 1000 (p = 0.036), below 100 (p = 0.028) and to be blast negative (p = 0.054), while GSTP1 GT haplotype and rs1138272 T allele carriers were more likely to be blasts positive (p = 0.034 and p = 0.024, respectively). ABCB1 CGT (rs1128503-rs2032582-rs1045642) haplotype carriers were more likely to be blast positive (p = 0.018). Conclusions Our results have shown that NR3C1 rs6198 variant and GSTP1 rs1695-rs1138272 haplotype are the most promising pharmacogenomic markers of GC response in ALL patients. |
| تدمد: | 1581-3207 |
| DOI: | 10.2478/raon-2018-0034 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c03d8b3ec91321cdb18cadbff2b36b11 https://doi.org/10.2478/raon-2018-0034 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c03d8b3ec91321cdb18cadbff2b36b11 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15813207 |
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| DOI: | 10.2478/raon-2018-0034 |