Three-dimensional Nuclear Telomere Organization in Multiple Myeloma

Klewes, Ludger; Vallente, Rhea U.; Dupas, Eric; Brand, Carolin; Grün, Dietrich; Guffei, Amanda; Sathitruangsak, Chirawadee; Awe, Julius Adebayo; Kuzyk, Alexandra; Lichtensztejn, Daniel; Tammur, Pille; Ilus, Tiiu; Tamm, Anu; Punab, Mari; Rubinger, Morel; Olujohungbe, Adebayo; Mai, Sabine

doi:10.1593/tlo.13613

Cited by 22 publications

(28 citation statements)

References 74 publications

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“…In comparison, normal lymphocyte nuclei had a smaller, rounder shape and emitted a brighter DAPI signal than myeloma nuclei [Klewes et al, 2013]. In this study, we have identified myeloma and lymphocyte nuclei based on size and intensity of the DAPI staining.…”

Section: Methodsmentioning

confidence: 79%

Quantitative Superresolution Microscopy Reveals Differences in Nuclear DNA Organization of Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

et al. 2015

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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. J. Cell. Biochem. 116: 704–710, 2015. © 2014 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.

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Section: Methodsmentioning

confidence: 79%

Quantitative Superresolution Microscopy Reveals Differences in Nuclear DNA Organization of Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

et al. 2015

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“…White blood cells were isolated as previously described . Briefly, 10 ml peripheral blood from each patient was collected in EDTA‐treated tubes.…”

Section: Methodsmentioning

confidence: 99%

“…White blood cells were isolated as previously described. 44 Briefly, 10 ml peripheral blood from each patient was collected in EDTA-treated tubes. Mononuclear cells were separated using Ficoll-Paque (GE Healthcare Life Sciences, Quebec, Canada) by a 30 min centrifugation at 200g.…”

Section: Isolation Of Lymphocytes and Myeloma Cellsmentioning

confidence: 99%

“…We previously identified myeloma cells based on green fluorescence signals emitted by the fluorescein isothiocyanate (FITC)-labeled CD138 antibody and on the size and intensity of the DAPI counterstained nucleus. 44,45 In comparison, normal lymphocyte nuclei have a smaller, rounder shape and emit a brighter DAPI signal than myeloma nuclei. In this study, we have identified myeloma and lymphocyte nuclei based on size and intensity of the DAPI staining.…”

Section: Identification Of Myeloma Cellsmentioning

confidence: 99%

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Distinct and shared three‐dimensional chromosome organization patterns in lymphocytes, monoclonal gammopathy of undetermined significance and multiple myeloma

Sathitruangsak

Righolt

Klewes

et al. 2016

Intl Journal of Cancer

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The consistent appearance of specific chromosomal translocations in multiple myeloma has suggested that the positioning of chromosomes in the interphase nucleus might play a role in the occurrence of particular chromosomal rearrangements associated with malignant transformation. Using fluorescence in situ hybridization, we have determined the positions of selected chromosome pairs (18 and 19, 9 and 22, 4 and 14, 14 and 16, 11 and 14) in interphase nuclei of myeloma cells compared to normal lymphocytes of treatment‐naïve patients. All chromosome pairs were arranged in a nonrandom pattern. Chromosomes commonly involved in myeloma‐associated translocations (4 and 14, 14 and 16, 11 and 14) were found in close spatial proximity, and this is correlated with the occurrence of overlapping chromosome territories. The spatial distribution of chromosomes may increase the possibility of chromosomal translocations in multiple myeloma.

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“…Equipped with such software, we have measured the 3D organization of telomeres in multiple cancers including HL, multiple myeloma, myelodysplastic syndromes and acute myeloid leukemia, glioblastoma, neuroblastoma, and prostate cancer [48][49][50][51][52][53] ( Figure 7). Nuclear genome changes do not only occur in cancer.…”

Section: Telomeresmentioning

confidence: 99%

The three‐dimensional cancer nucleus

Mai

2019

Genes Chromosomes & Cancer

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Research into the three‐dimensional (3D) organization of the cancer cell genome started over 100 years ago. We follow an exciting avenue of research in this field, from Hansemann's early observations of aberrant mitoses and nuclei in cancer cells in the late 19th century to Boveri's theory of the cancer cell in the early 20th century, to current views of nuclear organization and its changes in cancer. Molecular and imaging methods go hand in hand with providing us with a better understanding of the spatial nature of the cancer cell genome. This has led to the concept that the structural order of the nucleus can be used as cancer cell biomarker.

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Three-dimensional Nuclear Telomere Organization in Multiple Myeloma

Cited by 22 publications

References 74 publications

Quantitative Superresolution Microscopy Reveals Differences in Nuclear DNA Organization of Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

Quantitative Superresolution Microscopy Reveals Differences in Nuclear DNA Organization of Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

Distinct and shared three‐dimensional chromosome organization patterns in lymphocytes, monoclonal gammopathy of undetermined significance and multiple myeloma

The three‐dimensional cancer nucleus

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