Members of the glutathione and ABC-transporter families are associated with clinical outcome in patients with diffuse large B-cell lymphoma Journal Article

   

Authors:	Andreadis, C.; Gimotty, P. A.; Wahl, P.; Hammond, R.; Houldsworth, J.; Schuster, S. J.; Rebbeck, T. R.
Article Title:	Members of the glutathione and ABC-transporter families are associated with clinical outcome in patients with diffuse large B-cell lymphoma
Abstract:	Standard chemotherapy fails in 40% to 50% of patients with diffuse large B-cell lymphoma (DLBCL). Some of these failures can be salvaged with high-dose regimens, suggesting a role for drug resistance in this disease. We examined the expression of genes in the glutathione (GSH) and ATP-dependent transporter (ABC) families in 2 independent tissue-based expression microarray datasets obtained prior to therapy from patients with DLBCL. Among genes in the GSH family, glutathione peroxidase 1 (GPX1) had the most significant adverse effect on disease-specific overall survival (dOS) in the primary dataset (n = 130) (HR: 1.68; 95% CI: 1.26-2.22; P < .001). This effect remained statistically significant after controlling for biologic signature, LLMPP cellof-origin signature, and IPI score, and was confirmed in the validation dataset (n = 39) (HR: 1.7; 95% CI: 1.05-2.8; P = .033). Recursive partitioning identified a group of patients with low-level expression of GPX1 and multidrug resistance 1 (MDR1; ABCB1) without early treatment failures and with superior dOS (P < .001). Overall, our findings suggest an important association of oxidative-stress defense and drug elimination with treatment failure in DLBCL and identify GPX1 and ABCB1 as potentially powerful biomarkers of early failure and disease-specific survival. © 2007 by The American Society of Hematology.
Keywords:	cancer survival; treatment outcome; disease-free survival; survival rate; treatment failure; major clinical study; prednisone; doxorubicin; validation process; adjuvant therapy; cancer radiotherapy; gene expression; gene expression profiling; tumor markers, biological; cyclophosphamide; vincristine; drug resistance, neoplasm; b cell lymphoma; lymphoma, b-cell; statistical significance; microarray analysis; oligonucleotide array sequence analysis; abc transporter; predictive value of tests; glutathione; p-glycoprotein; gene expression regulation, leukemic; databases, genetic; multidrug resistance protein 1; membrane transport proteins; organic anion transporters; glutathione peroxidase 1; glutathione peroxidase; lymphoma, large-cell, diffuse
Journal Title:	Blood
Volume:	109
Issue:	8
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	2007-04-15
Start Page:	3409
End Page:	3416
Language:	English
DOI:	10.1182/blood-2006-09-047621
PUBMED:	17179223
PROVIDER:	scopus
PMCID:	PMC1852238
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-34147156300&partnerID=40&md5=ca56166c027179a4c86300f13493ffbc
Notes:	--- - "Cited By (since 1996): 15" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus"

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