Implication of IRF4 aberrant gene expression in the acute leukemias of childhood.

The most frequent targets of genetic alterations in human leukemias are transcription factor genes with essential functions in normal blood cell development. The Interferon Regulatory Factor 4 (IRF4) gene encodes a transcription factor important for key developmental stages of hematopoiesis, with kn...

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Autores principales:	Maria Adamaki, George I Lambrou, Anastasia Athanasiadou, Marianna Tzanoudaki, Spiros Vlahopoulos, Maria Moschovi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/250db6a46789427f8069c577552efbe8
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spelling	oai:doaj.org-article:250db6a46789427f8069c577552efbe82021-11-18T08:59:24ZImplication of IRF4 aberrant gene expression in the acute leukemias of childhood.1932-620310.1371/journal.pone.0072326https://doaj.org/article/250db6a46789427f8069c577552efbe82013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23977280/?tool=EBIhttps://doaj.org/toc/1932-6203The most frequent targets of genetic alterations in human leukemias are transcription factor genes with essential functions in normal blood cell development. The Interferon Regulatory Factor 4 (IRF4) gene encodes a transcription factor important for key developmental stages of hematopoiesis, with known oncogenic implications in multiple myeloma, adult leukemias and lymphomas. Very few studies have reported an association of IRF4 with childhood malignancy, whereas high transcript levels have been observed in the more mature immunophenotype of ALL. Our aim was to investigate the expression levels of IRF4 in the diagnostic samples of pediatric leukemias and compare them to those of healthy controls, in order to determine aberrant gene expression and whether it extends to leukemic subtypes other than the relatively mature ALL subpopulation. Quantitative real-time RT-PCR methodology was used to investigate IRF4 expression in 58 children with acute leukemias, 4 leukemic cell lines and 20 healthy children. We show that aberrant IRF4 gene expression is implicated in a variety of leukemic subtypes; higher transcript levels appear in the more immature B-common ALL subtype and in T-cell than in B-cell leukemias, with the highest expression levels appearing in the AML group. Interestingly, we show that childhood leukemia, irrespective of subtype or cell maturation stage, is characterised by a minimum of approximately twice the amount of IRF4 gene expression encountered in healthy children. A statistically significant correlation also appeared to exist between high IRF4 expression and relapse. Our results show that ectopic expression of IRF4 follows the reverse expression pattern of what is encountered in normal B-cell development and that there might be a dose-dependency of childhood leukemia for aberrantly expressed IRF4, a characteristic that could be explored therapeutically. It is also suggested that high IRF4 expression might be used as an additional prognostic marker of relapse at diagnosis.Maria AdamakiGeorge I LambrouAnastasia AthanasiadouMarianna TzanoudakiSpiros VlahopoulosMaria MoschoviPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72326 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria Adamaki George I Lambrou Anastasia Athanasiadou Marianna Tzanoudaki Spiros Vlahopoulos Maria Moschovi Implication of IRF4 aberrant gene expression in the acute leukemias of childhood.
description	The most frequent targets of genetic alterations in human leukemias are transcription factor genes with essential functions in normal blood cell development. The Interferon Regulatory Factor 4 (IRF4) gene encodes a transcription factor important for key developmental stages of hematopoiesis, with known oncogenic implications in multiple myeloma, adult leukemias and lymphomas. Very few studies have reported an association of IRF4 with childhood malignancy, whereas high transcript levels have been observed in the more mature immunophenotype of ALL. Our aim was to investigate the expression levels of IRF4 in the diagnostic samples of pediatric leukemias and compare them to those of healthy controls, in order to determine aberrant gene expression and whether it extends to leukemic subtypes other than the relatively mature ALL subpopulation. Quantitative real-time RT-PCR methodology was used to investigate IRF4 expression in 58 children with acute leukemias, 4 leukemic cell lines and 20 healthy children. We show that aberrant IRF4 gene expression is implicated in a variety of leukemic subtypes; higher transcript levels appear in the more immature B-common ALL subtype and in T-cell than in B-cell leukemias, with the highest expression levels appearing in the AML group. Interestingly, we show that childhood leukemia, irrespective of subtype or cell maturation stage, is characterised by a minimum of approximately twice the amount of IRF4 gene expression encountered in healthy children. A statistically significant correlation also appeared to exist between high IRF4 expression and relapse. Our results show that ectopic expression of IRF4 follows the reverse expression pattern of what is encountered in normal B-cell development and that there might be a dose-dependency of childhood leukemia for aberrantly expressed IRF4, a characteristic that could be explored therapeutically. It is also suggested that high IRF4 expression might be used as an additional prognostic marker of relapse at diagnosis.
format	article
author	Maria Adamaki George I Lambrou Anastasia Athanasiadou Marianna Tzanoudaki Spiros Vlahopoulos Maria Moschovi
author_facet	Maria Adamaki George I Lambrou Anastasia Athanasiadou Marianna Tzanoudaki Spiros Vlahopoulos Maria Moschovi
author_sort	Maria Adamaki
title	Implication of IRF4 aberrant gene expression in the acute leukemias of childhood.
title_short	Implication of IRF4 aberrant gene expression in the acute leukemias of childhood.
title_full	Implication of IRF4 aberrant gene expression in the acute leukemias of childhood.
title_fullStr	Implication of IRF4 aberrant gene expression in the acute leukemias of childhood.
title_full_unstemmed	Implication of IRF4 aberrant gene expression in the acute leukemias of childhood.
title_sort	implication of irf4 aberrant gene expression in the acute leukemias of childhood.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/250db6a46789427f8069c577552efbe8
work_keys_str_mv	AT mariaadamaki implicationofirf4aberrantgeneexpressionintheacuteleukemiasofchildhood AT georgeilambrou implicationofirf4aberrantgeneexpressionintheacuteleukemiasofchildhood AT anastasiaathanasiadou implicationofirf4aberrantgeneexpressionintheacuteleukemiasofchildhood AT mariannatzanoudaki implicationofirf4aberrantgeneexpressionintheacuteleukemiasofchildhood AT spirosvlahopoulos implicationofirf4aberrantgeneexpressionintheacuteleukemiasofchildhood AT mariamoschovi implicationofirf4aberrantgeneexpressionintheacuteleukemiasofchildhood
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Implication of IRF4 aberrant gene expression in the acute leukemias of childhood.

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