Expression of the ALK protein by anaplastic large-cell lymphomas correlates with high proliferative activity

A variable fraction of anaplastic large-cell lymphomas (ALCLs) exhibits a t(2;5)(p23;q35) translocation that results in expression of the chimeric hyperphosphorylated protein NPM-ALK (p80). Tumor cells expressing NPM-ALK exhibit markedly enhanced proliferative activity, but comparative cellular kinetic studies on ALK+ (ALK lymphomas) and ALK-lymphomas are lacking. The present study showed that ALK+ lymphomas, detected with the monoclonal antibody ALKc (n = 17), had significantly higher average values for the proliferation-associated parameters mitotic index, ana/telophase index, growth index (x x mitotic index - apoptotic index, assuming x = 3), percentages of Ki-67+ cells and fraction of cells expressing cyclin A or B or the cell cycle-regulatory protein p34(cdc2) than did ALK- ALCLs (n = 15). Whether this intense proliferative activity contributes to the good response to chemotherapy and favorable outcome of ALK- ALCLs remains to be assessed in a larger series of patients. Our findings support the notion that ALK+ and ALK- ALCLs are 2 distinct disease entities.