title: Quantitative superresolution microscopy reveals differences in nuclear DNA organization of multiple myeloma and monoclonal gammopathy of undetermined significance.
abstract: The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three-dimensional structured illumination microscopy (3D-SIM) increases the spatial resolution beyond the limits of conventional widefield fluorescence microscopy. 3D-SIM reveals new insights into the nuclear architecture of cancer as we show for the first time that it resolves organizational differences in intranuclear DNA organization of myeloma cells in MGUS and in MM patients. In addition, we report a significant increase in nuclear submicron DNA structure and structure of the DNA-free space in myeloma nuclei compared to normal lymphocyte nuclei. Our study provides previously unknown details of the nanoscopic DNA architecture of interphase nuclei of the normal lymphocytes, MGUS and MM cells. This study opens new avenues to understanding the disease progression from MGUS to MM.
authors.affiliation: Manitoba Institute of Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Manitoba, Canada; Division of Medical Oncology, Department of Internal Medicine, Prince of Songkla University, Songkhla, Thailand.
authors.forename: Chirawadee
authors.initials: C
authors.lastname: Sathitruangsak
authors.forename: Christiaan H
authors.initials: CH
authors.lastname: Righolt
authors.forename: Ludger
authors.initials: L
authors.lastname: Klewes
authors.forename: Pille
authors.initials: P
authors.lastname: Tammur
authors.forename: Tiiu
authors.initials: T
authors.lastname: Ilus
authors.forename: Anu
authors.initials: A
authors.lastname: Tamm
authors.forename: Mari
authors.initials: M
authors.lastname: Punab
authors.forename: Adebayo
authors.initials: A
authors.lastname: Olujohungbe
authors.forename: Sabine
authors.initials: S
authors.lastname: Mai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000648:ultrastructure*; D004247:DNA / Q000648:ultrastructure*; D006801:Humans; D008214:Lymphocytes / Q000648:ultrastructure; D008853:Microscopy; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000235:genetics / Q000473:pathology*; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology*
chemical_list: D004247:DNA
keywords: 3D STRUCTURED ILLUMINATION MICROSCOPY; DNA NANO STRUCTURE; MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE; MULTIPLE MYELOMA