TY - JOUR
T1 - Dynamics of microvesicle generation in B-cell chronic lymphocytic leukemia
T2 - Implication in disease progression
AU - Boysen, J.
AU - Nelson, M.
AU - Magzoub, G.
AU - Maiti, G. P.
AU - Sinha, S.
AU - Goswami, M.
AU - Vesely, S. K.
AU - Shanafelt, T. D.
AU - Kay, N. E.
AU - Ghosh, A. K.
N1 - Publisher Copyright:
© 2017 Macmillan Publishers Limited, part of Springer Nature.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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.
AB - 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.
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U2 - 10.1038/leu.2016.217
DO - 10.1038/leu.2016.217
M3 - Article
C2 - 27480387
AN - SCOPUS:84990886723
SN - 0887-6924
VL - 31
SP - 350
EP - 360
JO - Leukemia
JF - Leukemia
IS - 2
ER -