CD38 signals upregulate expression and functions of matrix metalloproteinase-9 in chronic lymphocytic leukemia cells

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy characterized by the accumulation of a population of CD5+/CD23+ mature B lymphocytes in the peripheral blood, bone marrow and lymph nodes.1 In vivo studies have shown that a significant proportion of the leukemic clone renovates daily and that cell proliferation occurs almost exclusively in lymphoid organs. Here, an intense bi-directional crosstalk takes place between the CLL cell and surrounding non-neoplastic lymphoid and stromal elements. The lymph node architecture is then molded into an anatomically defined niche, known as the proliferation center, where the antigen(s) is presented to the neoplastic cell together with a cocktail of soluble and cell-bound accessory signals. The ensuing proliferation may lead to the acquisition of novel genetic lesions or to the expansion of pre-existing leukemic subclones harboring deleterious mutations.