Leuk Res. 2004 Oct;28(10):1043-51.

Elevated levels of soluble CD44 are associated with advanced disease
and in vitro proliferation of neoplastic lymphocytes in B-cell
chronic lymphocytic leukaemia.

Eisterer W, Bechter O, Soderberg O, Nilsson K, Terol M, Greil R,
Thaler J, Herold M, Finke L, Gunthert U, Montserrat E, Stauder R.

Department of General Internal Medicine, University Hospital,
Innsbruck, Austria.

Purpose: Increased expression of the adhesion molecule CD44 has been
associated with an unfavorable clinical outcome in lymphomas. We
evaluated the prognostic value of soluble CD44 in B-cell chronic
lymphocytic leukaemia (B-CLL) and analysed the source and regulation
of CD44 secretion in B-CLL clones in vitro.

Patients and methods: Levels of soluble CD44 standard (sCD44s) and of
the soluble variant isoform CD44v6 (sCD44v6) were analysed by enzyme
linked immuno sorbent assay. Highly purified B-CLL cells (98%- cells)
were stimulated in vitro by different combinations of thioredoxin
(Trx), Staphylococcus aureus Cowan strain 1 (SAC), IL-2, IL-4, IL-10,
12-O-tetradecanoyl-phorbol-13-acetate (TPA) and by anti-CD40 mAbs
presented on irradiated CD32L cells.

Results: Serum levels of sCD44s and of sCD44v6 are significantly
elevated in B-CLL patients in comparison with normal persons.
Elevated levels of sCD44s and sCD44v6 are associated with an advanced
disease as reflected by an extended lymph node involvement, an
advanced Binet and Rai stage and chemotherapy requirement.

High levels of sCD44s are associated with high leukocyte counts and
increased sCD44v6 is significantly associated with splenomegaly. In B-
CLL, sCD44s as well as sCD44v6 is shed from leukemia cells as shown
by in vitro cultures. Stimulation of B-CLL clones results in a
proliferation-associated increased secretion of sCD44s and of
sCD44v6.

B-CLL clones from advanced stage patients are characterised by an
increased capacity for proliferation and CD44 production in
comparison with early stage patients.

Conclusions: Both sCD44s and sCD44v6 represent a reliable prognostic
marker in B-CLL and may be involved in the pathogenesis of B-CLL.

PMID: 15289016 [PubMed - in process]