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Forum on Immunopathological Diseases and Therapeutics
SJR: 0.309 SNIP: 0.041 CiteScore™: 0.18

ISSN Print: 2151-8017
ISSN Online: 2151-8025

Archives: Volume 1, 2010 to Volume 7, 2016

Forum on Immunopathological Diseases and Therapeutics

DOI: 10.1615/ForumImmunDisTher.v1.i1-2.90
pages 127-139

Clinical Significance of YY1 Overexpression in Human Hematopoietic Malignancies

Sara Huerta-Yepez
Department of Microbiology, Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer Center, University of California, USA; Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez, SSA, Mexico City, Mexico
Loredana Militello
Department of Microbiology, Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA
Stavroula Baritaki
Department of Microbiology and Molecular Genetics, David Geffen School of Medicine, Jonnson Comprehensive Cancer Center, University of California(UCLA), USA
Clara M. Rivera Pazos
Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez. Mexico City
Ma del Lourdes Cabrera-Munoz
Departamento de Patologia, Hospital Infantil de Mexico, Federico Gomez
Mario I. Vega
Oncology Research Unit, Oncology Hospital Siglo XXI National Medical Center IMSS, Mexico City, Mexico; Department of Medicine, Hematology-Oncology Division, Greater Los Angeles VA Healthcare Center, David Geffen School of Medicine, University of California, Los Angeles
Massimo Libra
Section of Clinical Pathology and Molecular Oncology, Department of Biomedical Sciences, University of Catania, Catania, Italy
Grazia Malaponte
Department of Biomedical Sciences, University of Catania, Catania
Silvana Canevari
Fondazione IRCCS Istituto Nazionale dei Tumori; Unit of Molecular Therapies, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Giancarlo Castellano
Department of Biomedical Sciences, University of Catania, Catania
Haiming Chen
Institute for Myeloma and Bone Cancer Research, West Hollywood, CA, USA
James R. Berenson
Institute for Myeloma and Bone Cancer Research, West Hollywood, CA, USA

ABSTRACT

Patients with multiple myeloma (MM) develop resistance to conventional therapies. The underlying molecular mechanism responsible for resistance is not clear. We have reported in solid tumors that transcription factor Yin Yang 1 (YY1) is overexpressed and regulates tumor cell resistance to apoptotic stimuli induced by chemo- and immunotherapeutic drugs. Therefore, we hypothesized that MM may overexpress YY1 and that its overexpression may be a poor prognostic factor. This hypothesis was tested by using both MM cell lines and MM derived from patients' bone marrow samples. MM cell lines showed overexpression of YY1 by immunohistochemistry (IHC). Bone marrow samples from patients with MM showed overexpression of YY1 by IHC as compared with low levels of YY1 in normal bone marrow samples. The intensity and frequency of cells expressing YY1 in both the cytoplasm and nucleus was significantly higher among patients with progressive disease compared with patients with stable and responsive disease. These findings demonstrate that the expression of YY1 in MM may correlate with prognosis. Furthermore, the findings suggest YY1 as a therapeutic target for intervention in the reversal of resistance and prevention of disease progression in patients with MM.


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