title: Dynamics of microvesicle generation in B-cell chronic lymphocytic leukemia: implication in disease progression.
abstract: 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.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: J
authors.initials: J
authors.lastname: Boysen
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nelson
authors.affiliation: Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: G
authors.initials: G
authors.lastname: Magzoub
authors.affiliation: Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: G P
authors.initials: GP
authors.lastname: Maiti
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Goswami
authors.affiliation: Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Vesely
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Shanafelt
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: N E
authors.initials: NE
authors.lastname: Kay
authors.affiliation: Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Ghosh
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D018941:Antigens, CD19 / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000378:metabolism / Q000648:ultrastructure; D015415:Biomarkers; D000074301:CD52 Antigen; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000648:ultrastructure; D018450:Disease Progression; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D061665:Time-to-Treatment; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; D000951:Antigens, Neoplasm; D015415:Biomarkers; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins