title: Quantitative analysis of clonal bone marrow CD19+ B cells: use of B cell lineage trees to delineate their role in the pathogenesis of light chain amyloidosis.
abstract: Light chain amyloidosis (AL) is a bone marrow (BM) plasma cell neoplasia with systemic deposition of Ig light chain amyloid fibrils. Here, we report the identification of clonal CD19 B cells in the BM and the use of a novel mathematical algorithm to generate B cell lineage trees of the clonal CD19 B cells and CD138 plasma cells from the BM of AL patients to delineate the relationship between these two clonal populations. The CD19+ clonal B cells in the BM of AL patients related to the clonal plasma cells represent a pre-plasma cell precursor population. The B cell lineage trees from AL patients also show significant differences in clonal diversification and antigenic selection compared to clones from normal, healthy controls. These data provide a robust example of the use of graphical quantification methods in delineating the role of neoplastic precursors in the pathogenesis of hematopoietic malignancies.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Manske
authors.forename: Neta S
authors.initials: NS
authors.lastname: Zuckerman
authors.forename: Michael M
authors.initials: MM
authors.lastname: Timm
authors.forename: Stephanie
authors.initials: S
authors.lastname: Maiden
authors.forename: Hanna
authors.initials: H
authors.lastname: Edelman
authors.forename: Gitit
authors.initials: G
authors.lastname: Shahaf
authors.forename: Michal
authors.initials: M
authors.lastname: Barak
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.forename: Ramit
authors.initials: R
authors.lastname: Mehr
authors.forename: Roshini S
authors.initials: RS
authors.lastname: Abraham
mesh_terms: D000465:Algorithms; D000686:Amyloidosis / Q000276:immunology* / Q000473:pathology; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D001855:Bone Marrow Diseases / Q000276:immunology* / Q000473:pathology; D019070:Cell Lineage / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000276:immunology*; D016130:Immunophenotyping; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000235:genetics / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D053668:Syndecan-1; D053667:Syndecans
chemical_list: D018941:Antigens, CD19; D007147:Immunoglobulin Light Chains; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D012313:RNA