مورد إلكتروني
HDAC isoenzyme expression is deregulated in chronic lymphocytic leukemia B-cells and has a complex prognostic significance.
| العنوان: | HDAC isoenzyme expression is deregulated in chronic lymphocytic leukemia B-cells and has a complex prognostic significance. |
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| المصدر: | Epigenetics, 7 (12 |
| بيانات النشر: | 2012-12 |
| تفاصيل مُضافة: | Van Damme, Michaël Crompot, Emerence Meuleman, Nathalie Mineur, Philippe Bron, Dominique Lagneaux, Laurence Stamatopoulos, Basile |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Histone deacetylases (HDACs) play a crucial role in chromatin structure and, consequently, gene expression. Their deregulation has been reported in various cancers. We performed a complete and comprehensive study of the expression of 18 HDACs (including Sirtuin; SIRT) by real-time PCR in a cohort of 200 chronic lymphocytic leukemia (CLL) patients with a median follow-up of 77 mo, and compared it with the results obtained from normal B cells. We also compared HDAC expression at diagnosis and after relapse. We observed significant deregulation (mostly upregulation) of HDACs in CLL. In terms of clinical significance, only HDAC6 was significantly correlated with treatment-free survival (TFS), whereas HDAC3 and SIRT2, 3 and 6 were correlated with overall survival (OS). A multivariate Cox regression stepwise analysis indicated that HDAC6, 7 and 10 and SIRT3 were TFS independent predictors. Interestingly, poor prognosis was associated with an overexpression of HDAC7 and 10 but an underexpression of HDAC6 and SIRT3. Therefore, these factors were combined in a TFS score: patients with a score of 0-1-2, 3 and 4 had a median TFS of 107, 57 and 26 mo, respectively (HR = 4.03, p < 0.0001). For OS, SIRT5 and 6 allowed stratification into 3 groups, with a median OS of > 360, 237 and 94 mo (HR = 6.38, p < 0.0001). However, we could not find statistical differences in HDAC expression after relapse. These results, validated by a 5-fold cross-validation, highlight the complex impact of HDAC expression in CLL clinical course. Journal Article Research Support, Non-U.S. Gov't SCOPUS: ar.j info:eu-repo/semantics/published |
| مصطلحات الفهرس: | Cancérologie, Adult, Aged, Aged, 80 and over, B-Lymphocytes -- enzymology -- pathology, Case-Control Studies, Fetal Blood -- enzymology, Follow-Up Studies, Gene Expression Regulation, Leukemic, Histone Deacetylases -- genetics, Humans, Isoenzymes -- genetics, Leukemia, Lymphocytic, Chronic, B-Cell -- diagnosis -- enzymology -- genetics -- mortality, Middle Aged, Prognosis, Proportional Hazards Models, Reference Values, Reproducibility of Results, Sirtuin 3 -- genetics, Up-Regulation, Chronic lymphocytic leukemia, HDAC, Real-time PCR, Sirtuin, info:eu-repo/semantics/article, info:ulb-repo/semantics/articlePeerReview, info:ulb-repo/semantics/openurl/article |
| URL: | |
| الإتاحة: | Open access content. Open access content 1 full-text file(s): info:eu-repo/semantics/restrictedAccess |
| ملاحظة: | 1 full-text file(s): application/pdf English |
| أرقام أخرى: | EQY oai:dipot.ulb.ac.be:2013/144354 uri/info:doi/10.4161/epi.22674 uri/info:pii/22674 uri/info:pmid/23108383 uri/info:scp/84870750886 uri/info:pmcid/PMC3528695 855622176 |
| المصدر المساهم: | UNIVERSITE LIBRE DE BRUXELLES From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.ocn855622176 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |