Ikaros (IKZF1): From Normal Hematopoiesis to Hematologic Malignancies

Baghdadi, Hamed; Shakouri Khomartash, Mehdi; Ahmadi, Nazanin; Faridfar, Ali; Ghorbani, Mahdi

doi:10.61186/ijbc.16.1.21

Volume 16, Issue 1 (March 2024 2024) Iranian Journal of Blood and Cancer 2024, 16(1): 21-34 | Back to browse issues page

‎ 10.61186/ijbc.16.1.21

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Baghdadi H, Shakouri Khomartash M, Ahmadi N, Faridfar A, Ghorbani M. Ikaros (IKZF1): From Normal Hematopoiesis to Hematologic Malignancies. Iranian Journal of Blood and Cancer 2024; 16 (1) :21-34
URL: http://ijbc.ir/article-1-1483-en.html

Ikaros (IKZF1): From Normal Hematopoiesis to Hematologic Malignancies

Hamed Baghdadi¹

, Mehdi Shakouri Khomartash²

, Nazanin Ahmadi²

, Ali Faridfar³

, Mahdi Ghorbani ^*

⁴

1- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, AJA University of Medical Sciences, Tehran, 1411718541, Iran
2- Medical Biotechnology Research Center, AJA University of Medical Sciences, Tehran, 1411718541, Iran
3- AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, 1411718541, Iran
4- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, AJA University of Medical Sciences, Tehran, 1411718541, Iran , M.ghorbani@ajaums.ac.ir

Abstract: (176 Views)

Ikaros zinc finger (IKZF) transcription factors, part of the Krüppel family, have a significant role in the physiological development of immune cells. Ikaros, which is encoded by IKZF1, is a well-researched IKZF transcription factor that specifically impacts the growth and differentiation of lymphocytes. It interacts with various nuclear factors, functioning as either a transcriptional inhibitor or activator; thus, regulates several lymphopoiesis-associated factors like pre-TCR and pre-BCR. Over the years, research has revealed that alterations in IKZF1 as well as Ikaros can cause out-of-control differentiation and proliferation of immune cells, particularly lymphocytes, potentially triggering tumorigenesis in hematologic malignancies such as ALL, AML, CLL, and CML. Recent studies have explored the therapeutic potential of targeting Ikaros or restoring its activities to limit the pathologic differentiation and proliferation of tumor cells. Most of these therapeutic agents are immunomodulatory drugs (IMiDs) that can selectively ubiquitinate and proteasome degrade Ikaros. This study offers a comprehensive overview of Ikaros’s physiological roles and highlights the oncogenic characteristics of IKZF1 and Ikaros alterations.

Keywords: IKZF1, Ikaros, ALL, AML, Immunomodulatory drugs

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: Review Article | Subject: Genetics
Received: 2023/11/17 | Accepted: 2024/01/26 | Published: 2024/03/25

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