Tumor necrosis factor modulates CD 20 expression on cells from chronic lymphocytic leukemia: a new role for TNF alpha?
Tumor necrosis factor alpha (TNF alpha) is a pleiotropic cytokine that is constitutively produced by leukemic cells in B Chronic Lymphocytic Leukemia (B-CLL). It has been shown to have autocrine and paracrine functions in normal B cells and in B lymphoproliferative diseases. This study was conducted to determine the effect of TNF alpha (in vitro) on CD20 expression on cells from patients with B-CLL. Currently, anti-CD20 monoclonal antibody therapy is becoming a second line treatment in the management of B cell disorders like low-grade non-Hodgkin's lymphoma (NHL) and B-CLL. Our results demonstrate amply that very low doses of TNF alpha (0. 0125 ng/ml) can be used to significantly increase CD20 expression on cells from patients of B-CLL as evidenced by increases in both percentage positivity and mean fluorescence intensity. The upregulation is evident as early as 24 hours and is maintained for up to 72 hours. We propose that the upregulation is a direct result of in vitro differentiation stimulated by TNF alpha. The results presented can be exploited in the designing of priming protocols prior to antibody therapy and this is discussed.
Sivaraman
S
S
Rush Cancer Institute, Rush Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612-3750, USA. ssivaram@rush.edu
Deshpande
C G
CG
Ranganathan
R
R
Huang
X
X
Jajeh
A
A
O'Brien
T
T
Huang
R W
RW
Gregory
S A
SA
Venugopal
P
P
Preisler
H D
HD
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018951:Antigens, CD20 / Q000032:analysis* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D014409:Tumor Necrosis Factor-alpha