INCREASED SERUM LEVELS OF SOLUBLE CD44 STANDARD BUT NOT OF VARIANT ISOFORMS V5 AND V6, IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA

The CD44 cell surface proteoglycan participates in a variety of functi ons including lymphohematopoiesis, lymphocyte homing and tumor metasta sis. In addition to the standard form (CD44st), a large family of vari ant isoforms (CD44v) is generated by alternative splicing of a single gene. Certain CD44v (v5 and V6) are upregulated in the course of neopl astic progression and reflect the metastatic potential of tumor cells. CD44 v6 is expressed in high-grade non-Hodgkin's lymphoma cells and i s released in the serum, thus providing a soluble marker that reflects tumor burden, disease progression and treatment response. Here we sho w that serum CD44st is elevated in approximately half of B-CLL patient s. In contrast, CD44v5 and v6 are detected at normal levels in the lar ge majority of the cases. CD44st serum levels correlate significantly with the number of circulating leukemic B cells and with the levels of another soluble B-CLL marker, beta(2)-microglobulin. Immunoprecipitat ion analyses of B-CLL sera allow detection of several high molecular w eight bands and of a 78 kDa band that represents a soluble form of CD4 4st and is 4 kDa lower than a similar band (82 kDa) detected in B-CLL cell lysates. Elevated serum CD44st associates with a number of unfavo rable prognostic factors such as high peripheral blood lymphocytosis, splenomegaly, advanced disease stage and therapy requirement. A follow -up study indicates that serum levels of CD44st are related to disease status, thus reinforcing our veiw that this molecule may represent a reliable tumor marker in B-CLL.