Phosphatase inhibition augments anti-CD22-mediated signaling and cytotoxicity in non-hodgkin's lymphoma cells

Robert T O'Donnell, David Pearson, Hayes C. McKnight, Ya Peng Ma, Joseph Tuscano

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

CD22 is a cell-surface molecule found on most B-cell lymphomas (NHL). HB22.7 is an anti-CD22 antibody that blocks CD22 ligand binding, initiates signaling, and kills NHL cells. The SHP-1 tyrosine phosphatase is disproportionately associated with the cytoplasmic domain of CD22. Sodium orthovanadate (NaV) and dephostatin (DP) are phosphatase inhibitors. The interaction of SHP-1 with CD22 presents an opportunity to manipulate CD22-mediated signaling effects. NaV caused dose dependent killing of NHL cells in vitro; when HB22.7 was given with NaV, antibody-mediated cell death increased. NaV caused a substantial increase in CD22-mediated SAPK and ERK-1/2 activation when CD22 was crosslinked by HB22.7; NaV did not significantly affect IgM-mediated signals. Studies using Raji NHL cells stably transfected with a SHP-1 dominant negative (DN) confirmed that these observations were due to SHP-1 inhibition. The relatively specific association of SHP-1 with CD22 suggests that CD22-specific signaling may be altered by phosphatase inhibition in ways that could prove useful for anti-CD22-based immunotherapy.

Original languageEnglish (US)
Pages (from-to)964-969
Number of pages6
JournalLeukemia Research
Volume33
Issue number7
DOIs
StatePublished - Jul 2009

Keywords

  • CD22
  • Lymphoma
  • Phosphatase inhibition

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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