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

Leuk Res. 2004 Oct;28(10):1043-51. doi: 10.1016/j.leukres.2004.01.016.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Cloning, Molecular
  • DNA / biosynthesis
  • Disease Progression
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Hyaluronan Receptors / blood
  • Hyaluronan Receptors / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Lymphocytes / immunology*
  • Lymphocytes / pathology
  • Predictive Value of Tests
  • Prognosis
  • Solubility
  • Tumor Cells, Cultured


  • Hyaluronan Receptors
  • DNA