PKC Plays Role in CD5 Mediated Survival of CLL Cells

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Leukemia Research

Volume 31, Issue 2 , February 2007, Pages 183-193

Copyright © 2006 Elsevier Ltd All rights reserved.

CD5 provides viability signals to B cells from a subset of B-CLL

patients by a mechanism that involves PKC

Gema -Chacona, A. Vargasb, Jordac, Marta Moradod,

Silvia doa, Trinidad -Donaireb, Ignacio Losada-Fernandeza,

Nerea Rebolledaa and Paloma -Aciegoa

aFundacion LAIR, Madrid, Spain

bServicio de Medicina Interna, Hospital Universitario Puerta de

Hierro, Madrid, Spain

cServicio de Hematologia, Hospital Clinico San , Madrid, Spain

dServicio de Hematologia, Hospital Universitario La Paz, Madrid,

Spain

Received 22 March 2006; revised 22 March 2006; accepted 27 March

2006. Available online 24 May 2006.

Abstract

B-chronic lymphocytic leukaemia (B-CLL) is a heterogeneous disease

characterized by an accumulation of B lymphocytes expressing CD5. To

date, the biological significance of this molecule in B-CLL B cells

remains to be elucidated.

In this study, we have analysed the functional consequences of the

binding of an anti-CD5 antibody on B-CLL B cells. To this purpose,

we have measured the percentage of viability of B-CLL B cells in the

presence or in the absence of anti-CD5 antibodies and also examined

some of the biochemical events downstream the CD5-signalling.

We demonstrate that anti-CD5 induces phosphorylation of protein

tyrosine kinases and protein kinase C (PKC), while no activation of

Akt/PKB and MAPKs is detected. This signalling cascade results in

viability in a group of patients in which we observe an increase of

Mcl-1 levels, whereas the levels of bcl-2, bcl-xL and XIAP do not

change. We also report that this pathway leads to IL-10 production,

an immunoregulatory cytokine that might act as an autocrine growth

factor for leukaemic B cells.

Inhibition of PKC prevents the induction of Mcl-1 and IL-10,

suggesting that the activation of PKC plays an important role in the

CD5-mediated survival signals in B cells from a subset of B-CLL

patients.