Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them

The Ikaros zing-finger family transcription factors (IKZF TFs) are important regulators of lymphocyte development and differentiation and are also highly expressed in B cell malignancies, including Multiple Myeloma (MM), where they are required for cancer cell growth and survival. Moreover, IKZF TFs...

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Main Authors:	Marco Cippitelli, Helena Stabile, Andrea Kosta, Sara Petillo, Angela Gismondi, Angela Santoni, Cinzia Fionda
Format:	Article
Language:	English
Published:	MDPI AG 2021-01-01
Series:	International Journal of Molecular Sciences
Subjects:	IKZF Ikaros Aiolos IMiDs Lenalidomide Multiple Myeloma
Online Access:	https://www.mdpi.com/1422-0067/22/3/1103

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spelling	doaj-b3a9413e2d6b4b1a8ddd9e108d9b35002021-01-23T00:05:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01221103110310.3390/ijms22031103Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find ThemMarco Cippitelli0Helena Stabile1Andrea Kosta2Sara Petillo3Angela Gismondi4Angela Santoni5Cinzia Fionda6Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyThe Ikaros zing-finger family transcription factors (IKZF TFs) are important regulators of lymphocyte development and differentiation and are also highly expressed in B cell malignancies, including Multiple Myeloma (MM), where they are required for cancer cell growth and survival. Moreover, IKZF TFs negatively control the functional properties of many immune cells. Thus, the targeting of these proteins has relevant therapeutic implications in cancer. Indeed, accumulating evidence demonstrated that downregulation of Ikaros and Aiolos, two members of the IKZF family, in malignant plasma cells as well as in adaptative and innate lymphocytes, is key for the anti-myeloma activity of Immunomodulatory drugs (IMiDs). This review is focused on IKZF TF-related pathways in MM. In particular, we will address how the depletion of IKZF TFs exerts cytotoxic effects on MM cells, by reducing their survival and proliferation, and concomitantly potentiates the antitumor immune response, thus contributing to therapeutic efficacy of IMiDs, a cornerstone in the treatment of this neoplasia.https://www.mdpi.com/1422-0067/22/3/1103IKZFIkarosAiolosIMiDsLenalidomideMultiple Myeloma
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Marco Cippitelli Helena Stabile Andrea Kosta Sara Petillo Angela Gismondi Angela Santoni Cinzia Fionda
spellingShingle	Marco Cippitelli Helena Stabile Andrea Kosta Sara Petillo Angela Gismondi Angela Santoni Cinzia Fionda Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them International Journal of Molecular Sciences IKZF Ikaros Aiolos IMiDs Lenalidomide Multiple Myeloma
author_facet	Marco Cippitelli Helena Stabile Andrea Kosta Sara Petillo Angela Gismondi Angela Santoni Cinzia Fionda
author_sort	Marco Cippitelli
title	Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them
title_short	Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them
title_full	Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them
title_fullStr	Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them
title_full_unstemmed	Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them
title_sort	role of aiolos and ikaros in the antitumor and immunomodulatory activity of imids in multiple myeloma: better to lose than to find them
publisher	MDPI AG
series	International Journal of Molecular Sciences
issn	1661-6596 1422-0067
publishDate	2021-01-01
description	The Ikaros zing-finger family transcription factors (IKZF TFs) are important regulators of lymphocyte development and differentiation and are also highly expressed in B cell malignancies, including Multiple Myeloma (MM), where they are required for cancer cell growth and survival. Moreover, IKZF TFs negatively control the functional properties of many immune cells. Thus, the targeting of these proteins has relevant therapeutic implications in cancer. Indeed, accumulating evidence demonstrated that downregulation of Ikaros and Aiolos, two members of the IKZF family, in malignant plasma cells as well as in adaptative and innate lymphocytes, is key for the anti-myeloma activity of Immunomodulatory drugs (IMiDs). This review is focused on IKZF TF-related pathways in MM. In particular, we will address how the depletion of IKZF TFs exerts cytotoxic effects on MM cells, by reducing their survival and proliferation, and concomitantly potentiates the antitumor immune response, thus contributing to therapeutic efficacy of IMiDs, a cornerstone in the treatment of this neoplasia.
topic	IKZF Ikaros Aiolos IMiDs Lenalidomide Multiple Myeloma
url	https://www.mdpi.com/1422-0067/22/3/1103
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Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them

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