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 - Funding Information:
This work was supported by a RO1 research fund from the National Cancer Institute CA170006 and partly, by a fund from the CLL Global Research Foundation to AKG. We wish to acknowledge the contribution of all the CLL patients who consented and donated blood samples at the time of their visits to the Mayo Clinic, Rochester, MN, USA and the Stephenson Cancer Center, Oklahoma City, OK, USA.
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
VL - 31
SP - 350
EP - 360
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 2
ER -