Hypoxia inducible factor-alpha activation in lymphoma and relationship to the thioredoxin family
British Journal of Haematology
Hypoxia inducible factor; Lymphoma; Prognosis; Thioredoxin; Tissue microarray
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.
Evens, A., Schumacker, P., Helenowski, I., Singh, A., Dokic, D., Keswani, A., Kordeluk, E., Raji, A., Winter, J., Jovanovic, B., Holmgren, A., Nelson, B., & Gordon, L. (2008). Hypoxia inducible factor-alpha activation in lymphoma and relationship to the thioredoxin family. British Journal of Haematology, 141 (5). http://dx.doi.org/10.1111/j.1365-2141.2008.07093.x