Investigators aimed to assess mechanisms through which CD38 regulates CLL homing and determine contribution of enzymatic activities of CD38 in leukemic environment

Mec-1 cell line genetically modified to obtain CD38+ clones (CD38wt) and mutant CD38 clones

CD38wt cells: higher growth rate and metastatic potential, higher weight decrease, more pronounced involvement of target organs, such as kidney

CD38wt cell line: up-modulation of several genes involved in chemotaxis, adhesion and signaling pathways, hence clones had higher migratory behavior and adhesive properties

Treatment with kuromanin (specific inhibitor of CD38 enzymatic activities): inhibited production of CD38 metabolites, reduced chemotactic ability of CLL cells in response to CXCL12

Enzymatic activities of CD38 play major role in regulation of CLL growth and homing

CD38 can be potential therapeutic target using monoclonal antibodies or enzyme inhibitors