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Volume 22
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10.3390/ijms22031103
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Review

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

by
Marco Cippitelli
1,*,
Helena Stabile
1,
Andrea Kosta
1,
Sara Petillo
1,
Angela Gismondi
1,
Angela Santoni
1,2 and
Cinzia Fionda
1,*
1
Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
2
IRCCS Neuromed–Instituto Neurologico Mediterraneo, 86077 Pozzilli, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(3), 1103; https://doi.org/10.3390/ijms22031103
Submission received: 28 December 2020 / Revised: 17 January 2021 / Accepted: 19 January 2021 / Published: 22 January 2021
(This article belongs to the Special Issue Transcription Factors in Cancer)
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Abstract

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.
Keywords: IKZF; Ikaros; Aiolos; IMiDs; Lenalidomide; Multiple Myeloma IKZF; Ikaros; Aiolos; IMiDs; Lenalidomide; Multiple Myeloma

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MDPI and ACS Style

Cippitelli, M.; Stabile, H.; Kosta, A.; Petillo, S.; Gismondi, A.; Santoni, A.; Fionda, C. Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them. Int. J. Mol. Sci. 2021, 22, 1103. https://doi.org/10.3390/ijms22031103

AMA Style

Cippitelli M, Stabile H, Kosta A, Petillo S, Gismondi A, Santoni A, Fionda C. 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. 2021; 22(3):1103. https://doi.org/10.3390/ijms22031103

Chicago/Turabian Style

Cippitelli, Marco, Helena Stabile, Andrea Kosta, Sara Petillo, Angela Gismondi, Angela Santoni, and Cinzia Fionda. 2021. "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 22, no. 3: 1103. https://doi.org/10.3390/ijms22031103

APA Style

Cippitelli, M., Stabile, H., Kosta, A., Petillo, S., Gismondi, A., Santoni, A., & Fionda, C. (2021). 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, 22(3), 1103. https://doi.org/10.3390/ijms22031103

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