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

被引：46

作者：

Evens, Andrew M. ^{[1
,2
]}

Schumacker, Paul T. ^{[2
,3
]}

Helenowski, Irene B. ^{[2
,4
]}

Singh, Amareshwar T. K. ^{[2
]}

Dokic, Danijela ^{[2
,3
]}

Keswani, Anjeni ^{[2
]}

Kordeluk, Elizabeth ^{[1
,2
]}

Raji, Adekunle ^{[2
,5
]}

Winter, Jane N. ^{[1
,2
]}

Jovanovic, Borko D. ^{[2
,4
]}

Holmgren, Arne ^{[6
]}

Nelson, Beverly P. ^{[2
,5
]}

Gordon, Leo I. ^{[1
,2
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Lymphoma Program, Div Hematol Oncol, Chicago, IL 60611 USA

[2] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

[3] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA

[4] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA

[5] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA

[6] Karolinska Inst, Dept Med Biochem & Biophys, Med Nobel Inst Biochem, Stockholm, Sweden

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2008年 / 141卷 / 05期

关键词：

hypoxia inducible factor; thioredoxin; lymphoma; prognosis; tissue microarray;

D O I：

10.1111/j.1365-2141.2008.07093.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Hypoxia inducible factors (HIFs) activate oncogenic pathways, while thioredoxins (Trx), including Trx1 and Trx reductases-1 and -2 (TrxR1 and TrxR2), promote HIF-alpha stabilization. In immunoblotting studies in lymphoma cell lines we found that Raji and SUDHL4 cells exhibited normoxic HIF-2 alpha 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-1 alpha and HIF-2 alpha, P = 0.0017). These data demonstrate that HIF and the thioredoxin family are abnormally activated in lymphoma.

引用

页码：676 / 680

页数：5

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