Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation: Induction of bax

Jamie L. Szocinski, Annette R. Khaled, Julie Hixon, Douglas Halverson, Satoshi Funakoshi, William C. Fanslow, Ann Boyd, Dennis D. Taub, Scott K. Durum, Clay B. Siegall, Dan L. Longo, William J Murphy

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

CD40 is present on both normal and neoplastic B-lineage cells. CD40 stimulation of normal B cells has been shown to promote normal growth and differentiation, whereas aggressive histology B lymphomas are growth inhibited. The inhibition of neoplastic B-cell growth is believed to occur via activation-induced cell death in which stimuli that typically promote the growth of normal cells prevent the growth of their neoplastic counterparts. We show here that CD40 stimulation using either a soluble recombinant human CD40 ligand (srhCD40L) or anti-CD40 monoclonal antibody resulted in apoptosis of human Burkitt lymphoma cell lines. Additional studies examining the mechanism of CD40-mediated death revealed an increase in bax messenger RNA with a subsequent increase in Bax protein in the mitochondria of the treated cells. In vitro exposure of the cells to bax antisense oligonucleotides resulted in a significant decline in Bax protein levels and partial protection from CD40-mediated death, indicating that induction of Bax was at least one mechanism underlying this inhibitory effect of CD40 stimulation on lymphomas. When immunodeficient mice bearing Burkitt lymphoma were treated with srhCD40L, significant increases in survival were observed indicating a direct antitumor effect as a result of CD40 stimulation in vivo. Overall, these results demonstrate that CD40 ligation of aggressive histology B-lymphoma cells results in inhibition both in vitro and in vivo and thus may be of potential clinical use in their treatment.

Original languageEnglish (US)
Pages (from-to)217-223
Number of pages7
JournalBlood
Volume100
Issue number1
DOIs
StatePublished - Jul 1 2002
Externally publishedYes

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Histology
Cell death
Lymphoma
Cell Death
Chemical activation
Cells
bcl-2-Associated X Protein
CD40 Ligand
Growth
Burkitt Lymphoma
Bearings (structural)
B-Lymphocytes
Mitochondria
Antisense Oligonucleotides
Cell growth
B-Cell Lymphoma
Monoclonal Antibodies
Ligation
Apoptosis
Messenger RNA

ASJC Scopus subject areas

  • Hematology

Cite this

Szocinski, J. L., Khaled, A. R., Hixon, J., Halverson, D., Funakoshi, S., Fanslow, W. C., ... Murphy, W. J. (2002). Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation: Induction of bax. Blood, 100(1), 217-223. https://doi.org/10.1182/blood.V100.1.217

Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation : Induction of bax. / Szocinski, Jamie L.; Khaled, Annette R.; Hixon, Julie; Halverson, Douglas; Funakoshi, Satoshi; Fanslow, William C.; Boyd, Ann; Taub, Dennis D.; Durum, Scott K.; Siegall, Clay B.; Longo, Dan L.; Murphy, William J.

In: Blood, Vol. 100, No. 1, 01.07.2002, p. 217-223.

Research output: Contribution to journalArticle

Szocinski, JL, Khaled, AR, Hixon, J, Halverson, D, Funakoshi, S, Fanslow, WC, Boyd, A, Taub, DD, Durum, SK, Siegall, CB, Longo, DL & Murphy, WJ 2002, 'Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation: Induction of bax', Blood, vol. 100, no. 1, pp. 217-223. https://doi.org/10.1182/blood.V100.1.217
Szocinski JL, Khaled AR, Hixon J, Halverson D, Funakoshi S, Fanslow WC et al. Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation: Induction of bax. Blood. 2002 Jul 1;100(1):217-223. https://doi.org/10.1182/blood.V100.1.217
Szocinski, Jamie L. ; Khaled, Annette R. ; Hixon, Julie ; Halverson, Douglas ; Funakoshi, Satoshi ; Fanslow, William C. ; Boyd, Ann ; Taub, Dennis D. ; Durum, Scott K. ; Siegall, Clay B. ; Longo, Dan L. ; Murphy, William J. / Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation : Induction of bax. In: Blood. 2002 ; Vol. 100, No. 1. pp. 217-223.
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