title: Chromosomal aberrations are shared by malignant plasma cells and a small fraction of circulating CD19+ cells in patients with myeloma and monoclonal gammopathy of undetermined significance.
abstract: In the present study, we aimed to identify distinct structural and numerical chromosomal aberrations in peripheral blood B cells of patients with myeloma and monoclonal gammopathy of undetermined significance (MGUS), which reflect changes thought to occur at different stages of the disease process. Peripheral blood from 12 patients with multiple myeloma and three patients with MGUS was investigated for the occurrence of retinoblastoma-1 gene deletions, p53 gene deletions and numerical aberrations demonstrated previously to be present in the patients' bone marrow CD138+ cells. By combining immunocytochemical staining for light chains and interphase fluorescence in situ hybridization (FISH), aberrant light-chain +ve cells were detected in the circulating CD19+ cell fraction. Each kind of chromosomal change present in the myeloma tumour cells was found to be shared by a small fraction of CD19+ cells (0.1-1.8%; median 0.36%, n = 6). In one MGUS patient, aberrant cells could be identified with a frequency of 0.34% within the CD19-sorted cell fraction. Clonotypic cells were detected with a frequency of 0.01-0.07% of peripheral blood nucleated cells by m-RNA in situ hybridization with patient-specific probes in three investigated patients. These results provide evidence that the circulating clonotypic B cells are closely related to the malignant plasma cells in myeloma and MGUS.
authors.affiliation: First Department of Internal Medicine and Medical Oncology, Wilhelminenspital, University of Vienna, Montleartstrasse 37, 1160 Vienna, Austria.
authors.forename: Niklas
authors.initials: N
authors.lastname: Zojer
authors.forename: Judith
authors.initials: J
authors.lastname: Schuster-Kolbe
authors.forename: Irene
authors.initials: I
authors.lastname: Assmann
authors.forename: Jutta
authors.initials: J
authors.lastname: Ackermann
authors.forename: Kathrin
authors.initials: K
authors.lastname: Strasser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hübl
authors.forename: Johannes
authors.initials: J
authors.lastname: Drach
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018941:Antigens, CD19 / Q000276:immunology*; D001856:Bone Marrow Examination; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D002999:Clone Cells; D018450:Disease Progression; D004220:Disulfides; D017353:Gene Deletion; D005803:Genes, Immunoglobulin; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D006801:Humans; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology; D010265:Paraproteinemias / Q000235:genetics* / Q000276:immunology; D010649:Phenylalanine / Q000031:analogs & derivatives*; D010950:Plasma Cells / Q000502:physiology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011509:Proteoglycans; D012333:RNA, Messenger / Q000032:analysis; D053668:Syndecan-1; D053667:Syndecans; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
chemical_list: D018941:Antigens, CD19; D004220:Disulfides; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; C074024:RB 101; D010649:Phenylalanine