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Article: Reactive oxygen species activate differentiation gene transcription of acute myeloid leukemia cells via the JNK/c-JUN signaling pathway

TitleReactive oxygen species activate differentiation gene transcription of acute myeloid leukemia cells via the JNK/c-JUN signaling pathway
Authors
KeywordsAcute myeloid leukemia
JNK/c-JUN signaling pathway
Reactive oxygen species
Terminal differentiation
Issue Date2018
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/leukres
Citation
Leukemia Research, 2018, v. 68, p. 112-119 How to Cite?
AbstractReactive oxygen species (ROS) and altered cellular redox status are associated with many malignancies. Acute myeloid leukemia (AML) cells are maintained at immature state by differentiation blockade, which involves deregulation of transcription factors in myeloid differentiation. AML cells can be induced to differentiate by phorbol-12-myristate-13-acetate (PMA), which possesses pro-oxidative activity. However, the signaling events mediated by ROS in the activation of transcriptional program during AML differentiation has not been fully elucidated. Here, we investigated AML cell differentiation by treatment with PMA and ROS scavenger N-acetyl-l-cysteine (NAC). We observed elevation of intracellular ROS level in the PMA-treated AML cells, which correlated with differentiated cell morphology and increased CD11b+ mature cell population. The effect of PMA can be abolished by NAC co-treatment, supporting the involvement of ROS in the process. Moreover, we demonstrated that short ROS elevation mediated cell cycle arrest, but failed to activate myeloid gene transcription; whereas prolonged ROS elevation activated JNK/c-JUN signaling pathway. Inhibition of JNK suppressed the expression of key myeloid transcriptional regulators c-JUN, SPI-1 and MAFB, and prevented AML cells from undergoing terminal differentiation. These findings provide new insights into the crucial role of JNK/c-Jun signaling pathway in the activation of transcriptional program during ROS-mediated AML differentiation.
Persistent Identifierhttp://hdl.handle.net/10722/259088
ISSN
2015 Impact Factor: 2.606
2015 SCImago Journal Rankings: 1.043

 

DC FieldValueLanguage
dc.contributor.authorLam, CF-
dc.contributor.authorYeung, HT-
dc.contributor.authorLam, YM-
dc.contributor.authorNg, RK-
dc.date.accessioned2018-09-03T04:01:18Z-
dc.date.available2018-09-03T04:01:18Z-
dc.date.issued2018-
dc.identifier.citationLeukemia Research, 2018, v. 68, p. 112-119-
dc.identifier.issn0145-2126-
dc.identifier.urihttp://hdl.handle.net/10722/259088-
dc.description.abstractReactive oxygen species (ROS) and altered cellular redox status are associated with many malignancies. Acute myeloid leukemia (AML) cells are maintained at immature state by differentiation blockade, which involves deregulation of transcription factors in myeloid differentiation. AML cells can be induced to differentiate by phorbol-12-myristate-13-acetate (PMA), which possesses pro-oxidative activity. However, the signaling events mediated by ROS in the activation of transcriptional program during AML differentiation has not been fully elucidated. Here, we investigated AML cell differentiation by treatment with PMA and ROS scavenger N-acetyl-l-cysteine (NAC). We observed elevation of intracellular ROS level in the PMA-treated AML cells, which correlated with differentiated cell morphology and increased CD11b+ mature cell population. The effect of PMA can be abolished by NAC co-treatment, supporting the involvement of ROS in the process. Moreover, we demonstrated that short ROS elevation mediated cell cycle arrest, but failed to activate myeloid gene transcription; whereas prolonged ROS elevation activated JNK/c-JUN signaling pathway. Inhibition of JNK suppressed the expression of key myeloid transcriptional regulators c-JUN, SPI-1 and MAFB, and prevented AML cells from undergoing terminal differentiation. These findings provide new insights into the crucial role of JNK/c-Jun signaling pathway in the activation of transcriptional program during ROS-mediated AML differentiation.-
dc.languageeng-
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/leukres-
dc.relation.ispartofLeukemia Research-
dc.subjectAcute myeloid leukemia-
dc.subjectJNK/c-JUN signaling pathway-
dc.subjectReactive oxygen species-
dc.subjectTerminal differentiation-
dc.titleReactive oxygen species activate differentiation gene transcription of acute myeloid leukemia cells via the JNK/c-JUN signaling pathway-
dc.typeArticle-
dc.identifier.emailLam, YM: simonyuk@hku.hk-
dc.identifier.emailNg, RK: raykitng@hku.hk-
dc.identifier.authorityNg, RK=rp00273-
dc.identifier.doi10.1016/j.leukres.2018.03.012-
dc.identifier.pmid29609096-
dc.identifier.hkuros289778-
dc.identifier.volume68-
dc.identifier.spage112-
dc.identifier.epage119-
dc.publisher.placeUnited Kingdom-

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