Expression and phosphorylation of translation regulatory protein 4E-binding protein (BP)-1 in low-risk diffuse large B cell lymphoma

Mary J. Ninan, Ajay Rawal, Hector Mesa, Dennis J. Knapp, Michael A. Kuskowski, Pankaj Gupta

Research output: Contribution to journalArticlepeer-review

Abstract

Protein translation initiation is controlled by eukaryotic initiation factor 4E (eIF-4E) binding protein 1 (4E-BP1). Phosphorylated 4E-BP1 dissociates from eIF-4E, allowing translation of transcripts mediating cell cycling, survival, and angiogenesis. The expression and phosphorylation of 4E-BP1, and influence on prognosis of diffuse large B cell lymphoma (DLBCL), is unknown. Because at least some patients with low-risk (International Prognostic Index score 0-2) DLBCL treated with standard anthracycline-based chemotherapy experience a short survival, we examined if 4E-BP1 expression and phosphorylation may provide additional prognostic information in 35 patients with low-risk DLBCL. We examined their initial diagnostic pathology specimens for 4E-BP1 expression and phosphorylation using immunohistochemistry, and we correlated these with clinical outcomes. While 4E-BP1 was uniformly expressed, there was wide distribution in its level of phosphorylation (biological activity). 4E-BP1 phosphorylation correlated strongly with overall survival (OS; P = 0.007) and progression-free survival (PFS; P = 0.02) and was the most significant independent variable for both OS and PFS on multivariable analysis. Our findings suggest that immunohistochemical evaluation of 4E-BP1 phosphorylation may help refine the prognostication of patients with low-risk DLBCL. Prospective studies in an independent cohort of patients are warranted.

Original languageEnglish (US)
Pages (from-to)121-126
Number of pages6
JournalJournal of Hematopathology
Volume6
Issue number3
DOIs
StatePublished - Sep 2013

Bibliographical note

Funding Information:
Acknowledgments We thank Gloria A. Niehans, MD (Department of Pathology, VA Medical Center, Minneapolis, MN, USA) for providing archival samples for this study. This study was supported by the Veterans Health Administration.

Keywords

  • EIF4EBP1 protein, human
  • Eukaryotic initiation factor-4E
  • Lymphoma, large B cell, diffuse
  • Prognosis
  • Protein biosynthesis

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