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

Item Type:	Article
Title:	Elevated levels of soluble CD44 are associated with advanced disease and in vitro proliferation of neoplastic lymphocytes in B-cell chronic lymphocytic leukaemia
Creators Name:	Eisterer, W. and Bechter, O. and Soederberg, O. and Nilsson, K. and Terol, M. and Greil, R. and Thaler, J. and Herold, M. and Finke, L. and Guenthert, U. and Montserrat, E. and Stauder, R.
Abstract:	Purpose: Increased expression of the adhesion molecule CD44 has been associated with an unfavourable 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% CD19+CD3- 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 (n=90) in comparison with normal persons (n=44) (P<0.001). Elevated levels of sCD44s and sCD44v6 are associated with an advanced disease as reflected by an extended lymph node involvement (P<0.02), an advanced Binet (P<0.03) and Rai stage (P<0.04) and chemotherapy requirement (P<0.02). High levels of sCD44s are associated with high leukocyte counts (P<0.04) and increased sCD44v6 is significantly associated with splenomegaly (P<0.002). In B-CLL sCD44s as well as sCD44v6 is shed from leukaemia cells as shown by in vitro cultures. Stimulation of B-CLL clones results in a proliferation-associated increased secretion of sCD44s (rho=0.7; P=0.0001) and of sCD44v6 (rho=0.5; P=0.005). 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.
Keywords:	B-Cell Chronic Lymphocytic Leukaemia, B-CLL, CD44, CD44 Variant Isoforms, CD44v, HA, HEV, High-Endothelial Venules, Hyaluronate, NHL, Non-Hodgkin's Lymphoma, Prognosis, SCD44s, SCD44v6, Serum Marker, Soluble CD44s, Soluble CD44v6
Source:	Leukemia Research
ISSN:	0145-2126
Publisher:	Elsevier / Pergamon Press
Volume:	28
Number:	10
Page Range:	1043-1051
Date:	1 January 2004
Official Publication:	https://doi.org/10.1016/j.leukres.2004.01.016
PubMed:	View item in PubMed

Repository Staff Only: item control page