Evidence for a CD38+ active subset enriched in proliferating cells, within the clonal population in chronic lymphocytic leukemia patients

LB-340 Historically, chronic lymphocytic leukemia (B-CLL) is known as a lymphoid neoplasm characterized by the accumulation of CD5+ B cells showing morphologic features of resting cells. In the last decade several studies have revealed the existence of at least two clinically distinct subgroups among B-CLL cases. These cases can be distinguished by the existence of somatic mutations in Ig V genes and by their expression of cell activation markers such as CD38 and ZAP-70, which have now achieved prognostic significance. To assess which aspects of the immunobiology of B-CLL cells are impacted by expression of CD38 by clonal members within a B-CLL case we flow-sorted B-CLL cells from peripheral blood of 20 patients (% CD38 expression pre-sort, ranging from 1- 90%), into CD38- and CD38+ subsets and quantified telomere lengths as a measure of their replicative history. As a measure of cellular activation we studied telomerase activity in these flow-sorted cells. In addition, expression of activation-associated (CD27, CD69 and CD62L), signaling-associated (ZAP-70) and cell cycle-associated (Ki-67) markers were studied on CD38- and CD38+ cell subsets by immunofluorecence and multi-color flow cytometry in 95 cases (including those used for cell sorting experiments). Telomerase activity was markedly higher in the CD38+ subset compared to the CD38- subset in each case (p