Dynamics of microvesicle generation in B-cell chronic lymphocytic leukemia: implication in disease progression.

Previously, we reported that B-cell chronic lymphocytic leukemia (CLL) patients contained elevated levels of microvesicles (MVs). However, given the quiescent nature of CLL B-cells and the relative indolence of the disease, the dynamics of MV generation and their unique phenotypes are not clearly defined. In this study, we find that CLL B-cells generate MVs spontaneously and can be further induced by B-cell receptor-ligation. Most interestingly, CLL B-cells predominantly generate CD52 MVs, but not CD19 MVs in vitro, suggesting preferential usage of CD52 into leukemic-MVs and that the CLL plasma MV phenotypes corroborate well with the in vitro findings. Importantly, we detected increased accumulation of CD52 MVs in previously untreated CLL patients with progressive disease. Finally, sequential studies on MVs in pre- and post-therapy CLL patients demonstrate that although the plasma CD52 MV levels drop significantly after therapy in most and remain at low levels in some patients, a trend of increased accumulation of CD52 MVs was detected in majority of post-therapy CLL patients (25 of 33). In total, this study emphasizes that dynamic accumulation of CD52 MVs in plasma can be used to study CLL progression and may be a useful biomarker for patients as they progress and require therapy.