Title

Hypoxia inducible factor-alpha activation in lymphoma and relationship to the thioredoxin family

Document Type

Journal Article

Publication Date

6-1-2008

Journal

British Journal of Haematology

Volume

141

Issue

5

DOI

10.1111/j.1365-2141.2008.07093.x

Keywords

Hypoxia inducible factor; Lymphoma; Prognosis; Thioredoxin; Tissue microarray

Abstract

Hypoxia inducible factors (HIFs) activate oncogenic pathways, while thioredoxins (Trx), including Trx1 and Trx reductases-1 and -2 (TrxR1 and TrxR2), promote HIF-α stabilization. In immunoblotting studies in lymphoma cell lines we found that Raji and SUDHL4 cells exhibited normoxic HIF-2α protein stabilization. Five cell lines showed increased TrxR1 expression, while only Namalwa, HF1 and SUDHL4 had Trx1 and TrxR2 activation. Tissue microarrays in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) identified different HIF expression among histological subgroups (e.g. 44% DLBCL vs. 11% of FL cases with moderate-to-high expression of HIF-1α and HIF-2α, P = 0.0017). These data demonstrate that HIF and the thioredoxin family are abnormally activated in lymphoma. © 2008 The Authors.

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