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The dynamic functions of IRF4 in B cell malignancies

by Forghieri, Fabio , Pilato, Flora , Mesini, Nicolò , Tagliafico, Enrico , Fiorcari, Stefania , Trenti, Tommaso , Nasillo, Vincenzo , Lagreca, Ivana , Potenza, Leonardo , Marasca, Roberto , Barozzi, Patrizia , Riva, Giovanni , Maffei, Rossana , Martinelli, Silvia , Paolini, Ambra , Luppi, Mario , Atene, Claudio Giacinto

in Antigens / Apoptosis / Bone marrow / Cell cycle / Cell Differentiation / Cell growth / Chronic lymphocytic leukemia / Class switching / Deoxyribonucleic acid / DNA / DNA - metabolism / Gene expression / Germinal Center / Germinal centers / Hematology / Humans / Immunoglobulins / Interferon regulatory factor / Interferon regulatory factor 4 / Interferon Regulatory Factors - genetics / Interferon Regulatory Factors - metabolism / Internal Medicine / Kinases / Leukemia / Light / Lymphatic leukemia / Lymphocytes B / Malignancy / Medicine / Medicine & Public Health / Multiple myeloma / Neoplasms / Oncology / Plasma / Review / Transcription factors / Tumor suppressor genes / Tumors

2023

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2023

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2023

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Journal Article

The dynamic functions of IRF4 in B cell malignancies

Forghieri, Fabio,

Pilato, Flora,

Mesini, Nicolò,

Tagliafico, Enrico,

Fiorcari, Stefania,

Trenti, Tommaso,

Nasillo, Vincenzo,

Lagreca, Ivana,

Potenza, Leonardo,

Marasca, Roberto,

Barozzi, Patrizia,

Riva, Giovanni,

Maffei, Rossana,

Martinelli, Silvia,

Paolini, Ambra,

Luppi, Mario,

Atene, Claudio Giacinto

2023

Overview

The trajectory of B cell development goes through subsequent steps governed by complex genetic programs, strictly regulated by multiple transcription factors. Interferon regulatory factor 4 (IRF4) regulates key points from pre-B cell development and receptor editing to germinal center formation, class-switch recombination and plasma cell differentiation. The pleiotropic ability of IRF4 is mediated by its “kinetic control”, allowing different IRF4 expression levels to activate distinct genetic programs due to modulation of IRF4 DNA-binding affinity. IRF4 is implicated in B cell malignancies, acting both as tumor suppressor and as tumor oncogene in different types of precursors and mature B cell neoplasia. Here, we summarize the complexity of IRF4 functions related to different DNA-binding affinity, multiple IRF4-specific target DNA motif, and interactions with transcriptional partners. Moreover, we describe the unique role of IRF4 in acute leukemias and B cell mature neoplasia, focusing on pathogenetic implications and possible therapeutic strategies in multiple myeloma and chronic lymphocytic leukemia.

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Publisher

Springer International Publishing,Springer Nature B.V

Subject

/ Cell Differentiation

/ Cell growth

/ Chronic lymphocytic leukemia