Overexpression of Yin Yang 1 in bone marrow-derived human multiple myeloma and its clinical significance

Huerta-Yepez,Sara; Liu,Hong; Baritaki,Stavroula; Del Lourdes Cebrera‑Muñoz,Maria; Rivera-Pazos,Clara; Maldonado-Valenzuela,Altagracia; Valencia-Hipolito,Alberto; Vega,Mario  I.; Chen,Haiming; Berenson,James  R.; Bonavida,Benjamin

doi:10.3892/ijo.2014.2511

Overexpression of Yin Yang 1 in bone marrow-derived human multiple myeloma and its clinical significance

Authors:
- Sara Huerta-Yepez
- Hong Liu
- Stavroula Baritaki
- Maria Del Lourdes Cebrera‑Muñoz
- Clara Rivera-Pazos
- Altagracia Maldonado-Valenzuela
- Alberto Valencia-Hipolito
- Mario I. Vega
- Haiming Chen
- James R. Berenson
- Benjamin Bonavida
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Affiliations: Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA, Servicio de Patologia, Mexican Children Hospital ‘Federico Gomez’, Mexico City, Mexico, Oncology Disease Research Unit, Mexican Children Hospital ‘Federico Gomez, Mexico City, Mexico, Oncology Research Unit, Oncology Hospital, Siglo XXI National Medical Center IMSS, Mexico City, Mexico, Institute for Myeloma and Bone Cancer Research, Los Angeles, CA, USA
Published online on: June 20, 2014 https://doi.org/10.3892/ijo.2014.2511
Pages: 1184-1192

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Abstract

Multiple myeloma (MM) patients initially respond to conventional therapy, however, many develop resistance and have recurrences. We have reported in other tumors that the transcription factor Yin Yang 1 (YY1) is a resistant factor and, thus, we hypothesized that YY1 may be overexpressed in MM. Significantly, higher expression (staining intensity and cell frequency) of YY1 in MM cell lines and in bone marrow-derived (BM) MM from 22 MM patients was observed as compared to expression in normal BM. Higher nuclear YY1 staining was associated with disease progression. Bioinformatic analyses of mRNA in data sets corroborated the above findings and showed significant overexpression of YY1 in MM compared to normal tissues and other hematopoietic disorders. The role of YY1 expression in the regulation of drug resistance was exemplified in a drug-resistant MM cell line transfected with YY1 siRNA and which was shown to be sensitized to bortezomib-induced apoptosis. These findings highlight the potential prognostic significance of YY1 expression level in MM patients and as a therapeutic target.

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