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

Andrew Evens, Paul T. Schumacker, Irene B. Helenowski, Amareshwar T K Singh, Danijela Dokic, Anjeni Keswani, Elizabeth Kordeluk, Adekunle Raji, Jane N. Winter, Borko D. Jovanovic, Arne Holmgren, Beverly P. Nelson, Leo I. Gordon

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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.

Original languageEnglish (US)
Pages (from-to)676-680
Number of pages5
JournalBritish Journal of Haematology
Volume141
Issue number5
DOIs
StatePublished - Jun 1 2008

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All Science Journal Classification (ASJC) codes

  • Hematology

Keywords

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

Cite this

Evens, A., Schumacker, P. T., Helenowski, I. B., Singh, A. T. K., Dokic, D., Keswani, A., Kordeluk, E., Raji, A., Winter, J. N., Jovanovic, B. D., Holmgren, A., Nelson, B. P., & Gordon, L. I. (2008). Hypoxia inducible factor-alpha activation in lymphoma and relationship to the thioredoxin family. British Journal of Haematology, 141(5), 676-680. https://doi.org/10.1111/j.1365-2141.2008.07093.x