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 Citations (Scopus)

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

Fingerprint

Phosphoric Monoester Hydrolases
Non-Hodgkin's Lymphoma
Non-Receptor Type 6 Protein Tyrosine Phosphatase
Vanadates
B-Cell Lymphoma
Immunotherapy
Immunoglobulin M
Anti-Idiotypic Antibodies
Cell Death
Sodium
Ligands
Antibodies

Keywords

  • CD22
  • Lymphoma
  • Phosphatase inhibition

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Phosphatase inhibition augments anti-CD22-mediated signaling and cytotoxicity in non-hodgkin's lymphoma cells. / O'Donnell, Robert T; Pearson, David; McKnight, Hayes C.; Ma, Ya Peng; Tuscano, Joseph.

In: Leukemia Research, Vol. 33, No. 7, 07.2009, p. 964-969.

Research output: Contribution to journalArticle

@article{46121f70ca3e417ea1f4db40ccbb050f,
title = "Phosphatase inhibition augments anti-CD22-mediated signaling and cytotoxicity in non-hodgkin's lymphoma cells",
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.",
keywords = "CD22, Lymphoma, Phosphatase inhibition",
author = "O'Donnell, {Robert T} and David Pearson and McKnight, {Hayes C.} and Ma, {Ya Peng} and Joseph Tuscano",
year = "2009",
month = "7",
doi = "10.1016/j.leukres.2009.01.026",
language = "English (US)",
volume = "33",
pages = "964--969",
journal = "Leukemia Research",
issn = "0145-2126",
publisher = "Elsevier Limited",
number = "7",

}

TY - JOUR

T1 - Phosphatase inhibition augments anti-CD22-mediated signaling and cytotoxicity in non-hodgkin's lymphoma cells

AU - O'Donnell, Robert T

AU - Pearson, David

AU - McKnight, Hayes C.

AU - Ma, Ya Peng

AU - Tuscano, Joseph

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

KW - CD22

KW - Lymphoma

KW - Phosphatase inhibition

UR - http://www.scopus.com/inward/record.url?scp=67349230870&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349230870&partnerID=8YFLogxK

U2 - 10.1016/j.leukres.2009.01.026

DO - 10.1016/j.leukres.2009.01.026

M3 - Article

C2 - 19237192

AN - SCOPUS:67349230870

VL - 33

SP - 964

EP - 969

JO - Leukemia Research

JF - Leukemia Research

SN - 0145-2126

IS - 7

ER -