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

ISSN Druckformat: 2151-8017
ISSN Online: 2151-8025

Archives: Volume 1, 2010 to Volume 7, 2016

Forum on Immunopathological Diseases and Therapeutics

DOI: 10.1615/ForumImmunDisTher.2016017234
pages 141-151

Bifunctional Role of Kruppel-Like Factor 4 in Hematological Malignancies

Mario Morales-Martinez
Oncology Research Unit, Oncology Hospital Siglo XXI National Medical Center IMSS, Mexico City, Mexico
Luz A. Franco-Cea
Oncology Research Unit, Oncology Hospital Siglo XXI National Medical Center IMSS, Mexico City, Mexico
Liliana Moreno Vargas
Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez, SSA, Mexico City, Mexico
Otoniel Martinez-Maza
UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles
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
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

ABSTRAKT

Kruppel-like factor 4 (KLF4) is a member of the KLF zinc-finger−containing transcription factor family. Reported experimental data have indicated that KLF4 is either an oncogene or tumor suppressor. Moreover, other observations have indicated the role of KLF4 in the regulation of apoptosis, proliferation, and differentiation of B cells and B-cell malignancies. Interestingly, in contrast to adult lymphomas and most solid tumors, we have shown that KLF4 is overexpressed in pediatric non-Hodgkin lymphoma (NHL) tumor tissues, and overexpression of this protein predicted unresponsiveness to cyclophosphamide, doxorubicin, vincristine, and prednisolone treatment. Furthermore, we have found that the transcription factor Ying Yang 1 (YY1) is overexpressed in B-NHL and correlated with the expression of KLF4. Accordingly, we suggest that coexpression of KLF4 and YY1 may result from the transcriptional regulation of KLF4 by YY1. Indeed, this hypothesis was tested in various experimental designs that used both cell lines and tumor tissues derived from patients. From these findings, it was depicted that KLF4 and YY1 are regulated by microRNA-7 and that the activation of KLF4 can suppresses the extrinsic apoptotic pathway by inhibiting activation and cleavage of caspases 7, 9, and 3. Therefore, the overexpression of KLF4 in lymphoma may be responsible, in part, for pathogenesis, malignancy, and drug resistance. We propose that both KLF4 and YY1 may be prognostic biomarkers in pediatric lymphoma. Furthermore, the clinical testing of inhibitors of KLF4 may be a promising novel treatment for lymphoma.