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  1. Article: Genomic Landscape of Hodgkin Lymphoma.

    Brune, Magdalena M / Juskevicius, Darius / Haslbauer, Jasmin / Dirnhofer, Stefan / Tzankov, Alexandar

    Cancers

    2021  Volume 13, Issue 4

    Abstract: Background: Hodgkin lymphoma (HL) is predominantly composed of reactive, non-neoplastic cells surrounding scarcely distributed tumor cells, that is, so-called Hodgkin and Reed-Sternberg (HRS) or lymphocyte predominant (LP) cells. This scarcity impeded ... ...

    Abstract Background: Hodgkin lymphoma (HL) is predominantly composed of reactive, non-neoplastic cells surrounding scarcely distributed tumor cells, that is, so-called Hodgkin and Reed-Sternberg (HRS) or lymphocyte predominant (LP) cells. This scarcity impeded the analysis of the tumor cell genomes for a long time, but recently developed methods (especially laser capture microdissection, flow cytometry/fluorescence-activated cell sorting) facilitated molecular investigation, elucidating the pathophysiological principles of "Hodgkin lymphomagenesis".
    Methods: We reviewed the relevant literature of the last three decades focusing on the genomic landscape of classic and nodular lymphocyte predominant HL (NLPHL) and summarized molecular cornerstones.
    Results: Firstly, the malignant cells of HL evade the immune system by altered expression of
    Conclusion: The blueprint of HL genomics has been laid, paving the way for future investigations into its complex pathophysiology.
    Language English
    Publishing date 2021-02-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13040682
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: H3K27m3 overexpression as a new, BCL2 independent diagnostic tool in follicular and cutaneous follicle center lymphomas.

    Brune, Magdalena M / Vela, Visar / Bratic Hench, Ivana / Dertinger, Susanne / Borgmann, Vanessa / Dirnhofer, Stefan / Tzankov, Alexandar

    Virchows Archiv : an international journal of pathology

    2022  Volume 481, Issue 3, Page(s) 489–497

    Abstract: Approximately 15% of follicular lymphomas (FL) lack overexpression of BCL2 and the underlying translocation t(14;18). These cases can be diagnostically challenging, especially regarding follicular hyperplasia (FH). In a subset of FL, mutations in genes ... ...

    Abstract Approximately 15% of follicular lymphomas (FL) lack overexpression of BCL2 and the underlying translocation t(14;18). These cases can be diagnostically challenging, especially regarding follicular hyperplasia (FH). In a subset of FL, mutations in genes encoding for epigenetic modifiers, such as the histone-lysine N-methyltransferase EZH2 (enhancer of zeste homolog 2), were found, which might be used diagnostically. These molecular alterations can lead to an increased tri-methylation of histone H3 at position lysine 27 (H3K27m3) that, in turn, can be visualized immunohistochemically. The aim of this study was to analyze the expression of H3K27m3 in FL, primary cutaneous follicle center lymphomas (PCFCL), and pediatric-type FL (PTFL) in order to investigate its value in the differential diagnosis to FH and other B cell lymphomas and to correlate it to BCL2 expression and the presence of t(14;18). Additionally, the mutational profile of selected cases was considered to address H3K27m3's potential use as a surrogate parameter for mutations in genes encoding for epigenetic modifiers. Eighty-nine percent of FL and 100% of PCFCL cases overexpressed H3K27m3, independently of BCL2, EZH2, and the presence of mutations. In contrast, 95% of FH and 100% of PTFL cases lacked H3K27m3 overexpression. Other B cell lymphomas considered for differential diagnosis also showed overexpression of H3K27m3 in the majority of cases. In summary, overexpression of H3K27m3 can serve as a new, BCL2 independent marker in the differential diagnosis of FL and PCFCL, but not PTFL, to FH, while being not of help in the differential diagnosis of FL to other B cell lymphomas.
    MeSH term(s) Child ; Enhancer of Zeste Homolog 2 Protein/genetics ; Enhancer of Zeste Homolog 2 Protein/metabolism ; Histones/genetics ; Humans ; Lymphoma, B-Cell/diagnosis ; Lymphoma, B-Cell/genetics ; Lymphoma, B-Cell/metabolism ; Lymphoma, Follicular/diagnosis ; Lymphoma, Follicular/genetics ; Lymphoma, Follicular/pathology ; Lysine ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/metabolism
    Chemical Substances BCL2 protein, human ; Histones ; Proto-Oncogene Proteins c-bcl-2 ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; Lysine (K3Z4F929H6)
    Language English
    Publishing date 2022-06-04
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-022-03347-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud III Zs.10: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
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  3. Article: Molecular Progression of Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies.

    Brune, Magdalena M / Rau, Achim / Overkamp, Mathis / Flaadt, Tim / Bonzheim, Irina / Schürch, Christian M / Federmann, Birgit / Dirnhofer, Stefan / Fend, Falko / Tzankov, Alexandar

    Cancers

    2021  Volume 13, Issue 22

    Abstract: Myeloproliferative neoplasms (MPN) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) both harbor the potential to undergo myelodysplastic progression or acceleration and can transform into blast-phase MPN or MDS/MPN, a form of secondary acute ... ...

    Abstract Myeloproliferative neoplasms (MPN) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) both harbor the potential to undergo myelodysplastic progression or acceleration and can transform into blast-phase MPN or MDS/MPN, a form of secondary acute myeloid leukemia (AML). Although the initiating transforming events are yet to be determined, current concepts suggest a stepwise acquisition of (additional) somatic mutations-apart from the initial driver mutations-that trigger disease evolution. In this study we molecularly analyzed paired bone marrow samples of MPN and MDS/MPN patients with known progression and compared them to a control cohort of patients with stable disease course. Cases with progression displayed from the very beginning a higher number of mutations compared to stable ones, of which mutations in five (
    Language English
    Publishing date 2021-11-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13225605
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Effects of lenalidomide on the bone marrow microenvironment in acute myeloid leukemia: Translational analysis of the HOVON103 AML/SAKK30/10 Swiss trial cohort.

    Brune, Magdalena M / Stüssi, Georg / Lundberg, Pontus / Vela, Visar / Heim, Dominik / Manz, Markus G / Haralambieva, Eugenia / Pabst, Thomas / Banz, Yara / Bargetzi, Mario / Grobholz, Rainer / Fehr, Martin / Cogliatti, Sergio / Ossenkoppele, Gert J / Löwenberg, Bob / Rudolf, Christina Biaggi / Li, Qiyu / Passweg, Jakob / Mazzuchelli, Luca /
    Medinger, Michael / Tzankov, Alexandar

    Annals of hematology

    2021  Volume 100, Issue 5, Page(s) 1169–1179

    Abstract: This translational study aimed at gaining insight into the effects of lenalidomide in acute myeloid leukemia (AML). Forty-one AML patients aged 66 or older of the Swiss cohort of the HOVON-103 AML/SAKK30/10 study were included. After randomization, they ... ...

    Abstract This translational study aimed at gaining insight into the effects of lenalidomide in acute myeloid leukemia (AML). Forty-one AML patients aged 66 or older of the Swiss cohort of the HOVON-103 AML/SAKK30/10 study were included. After randomization, they received standard induction chemotherapy with or without lenalidomide. Bone marrow biopsies at diagnosis and before the 2nd induction cycle were obtained to assess the therapeutic impact on leukemic blasts and microenvironment. Increased bone marrow angiogenesis, as assessed by microvessel density (MVD), was found at AML diagnosis and differed significantly between the WHO categories. Morphological analysis revealed a higher initial MVD in AML with myelodysplasia-related changes (AML-MRC) and a more substantial decrease of microvascularization after lenalidomide exposure. A slight increase of T-bet-positive TH1-equivalents was identifiable under lenalidomide. In the subgroup of patients with AML-MRC, the progression-free survival differed between the two treatment regimens, showing a potential but not significant benefit of lenalidomide. We found no correlation between the cereblon genotype (the target of lenalidomide) and treatment response or prognosis. In conclusion, addition of lenalidomide may be beneficial to elderly patients suffering from AML-MRC, where it leads to a reduction of microvascularization and, probably, to an intensified specific T cell-driven anti-leukemic response.
    MeSH term(s) Aged ; Angiogenesis Inhibitors/therapeutic use ; Bone Marrow/blood supply ; Bone Marrow/drug effects ; Bone Marrow/pathology ; Cohort Studies ; Female ; Humans ; Lenalidomide/therapeutic use ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/pathology ; Male ; Neovascularization, Pathologic/drug therapy ; Neovascularization, Pathologic/pathology ; Tumor Microenvironment/drug effects
    Chemical Substances Angiogenesis Inhibitors ; Lenalidomide (F0P408N6V4)
    Language English
    Publishing date 2021-03-02
    Publishing country Germany
    Document type Journal Article ; Randomized Controlled Trial
    ZDB-ID 1064950-5
    ISSN 1432-0584 ; 0939-5555 ; 0945-8077
    ISSN (online) 1432-0584
    ISSN 0939-5555 ; 0945-8077
    DOI 10.1007/s00277-021-04467-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.181: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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