Growth Regulators Affect CLL Receptors; May Have Therapeutic Applications

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Leukemia 2002 Sep;16(9):1691-1698

Surface membrane antigen expression changes induced in

vitro by exogenous growth factors in chronic

lymphocytic leukemia cells.

Vilpo J, Hulkkonen J, Hurme M, Vilpo L.

Department of Clinical Chemistry, University of

Tampere Medical School and Laboratory Centre of

Tampere University Hospital, Tampere, Finland.

The factors determining the growth and survival of

cells in B chronic lymphocytic leukemia (CLL) have

remained poorly understood.

We investigated the effects of optimal mitogen

combinations (OMCs) on the expression of 26 surface

membrane antigens among 33 CLL patients. The seven

OMCs used were selected after pre-testing 14

combinations of (1) S. aureus Cowan I (SAC), (2)

interleukin-2 (IL-2), (3) tumor necrosis factor alpha

(TNF-alpha) and (4) 12-O-tetradecanoylphorbol

13-acetate (TPA; also known as phorbol 12-myristate

13-acetate or PMA).

In flow cytometry we revealed that OMCs induced

statistically highly significant upregulation of the

expression of CD5, CD11c, CD19, CD22, CD23, CD25,

CD38, CD40, CD45, CD45RO, CD95, CD126, CD130 and FMC7,

and downregulation of CD20 and CD124 expression.

Interestingly, the expression of CD27, CD45RA, CD79b,

CD80, CD122 and that of the immunoglobulin gene

superfamily members CD21, Ig-kappa, Ig-lambda,

Ig-delta and Ig- & mgr; were not significantly affected

under similar conditions.

The expression of several antigens was co-regulated,

suggesting common regulatory pathways. These antigens

include CD11c/CD5, CD11c/CD22, CD11c/CD126, CD11c/FMC7

as well as CD27/CD45, CD27/CD45RA and CD27/CD79b.

Upregulation of surface antigen expression, induced by

OMCs, should be applicable in antibody therapy in

vitro and in vivo, and in negative stem cell selection

for autotransplantation.

Furthermore, the current strategy to enhance cell

surface antigen expression may be a versatile tool to

raise humoral and cell-mediated host defense against

CLL cells. Upregulation of proteins mediating positive

growth signals (eg CD25, CD40) and negative signals or

apoptosis (eg CD95) may be used to sensitize cells to

chemotherapy and programmed cell death.

PMID: 12200683 [PubMed - as supplied by publisher]

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