Abstract:
PURPOSE:Pharmacological inhibition of mutant isocitrate dehydrogenase (IDH) reduces R-2-hydroxyglutarate (2-HG) levels and restores cellular differentiation in vivo and in vitro. The IDH2 inhibitor enasidenib (AG-221) has been approved by the FDA as a first-in-class inhibitor for the treatment of relapsed or refractory (R/R) IDH2-mutant acute myeloid leukemia (AML). In this study, the effects of a combination of all-trans retinoic acid (ATRA) and AG-221 on AML cell differentiation was explored, along with the mechanisms employed by IDH2-mutant cells in AML. MATERIALS AND METHODS:We treated the human AML cell line, IDH2-mutant-TF-1, and primary human AML cells carrying IDH2 mutation with 30 μM AG-221 and 100 nM ATRA, alone or in combination. RESULTS:Combined treatment with AG-221 and ATRA inhibited 2-HG production and resulted in synergistic effects on differentiation among IDH2-mutant AML cells and primary AML cells expressing IDH2 mutation. Combined treatment with AG-221 and ATRA altered autophagic activity. AG-221 and ATRA treatment-induced differentiation of IDH2-mutant AML cells was associated with autophagy induction, without suppressing autophagy flux at maturation and degradation stages. A RAF-1/MEK/ERK pathway was founded to be associated with AG-221 and ATRA-induced differentiation in IDH2-mutant AML cells. IDH-associated changes in histone methylation markers decreased after AG-221 and ATRA combination treatment. CONCLUSION:Our preliminary evidence indicates that the addition of ATRA to treatments with IDH2 inhibitor may lead to further improvements or increases in response rates in IDH2-mutant AML patients who do not appear to benefit from treatments with IDH2 inhibitor alone.
journal_name
Yonsei Med Jjournal_title
Yonsei medical journalauthors
Kim Y,Jeung HK,Cheong JW,Song J,Bae SH,Lee JI,Min YHdoi
10.3349/ymj.2020.61.9.762subject
Has Abstractpub_date
2020-09-01 00:00:00pages
762-773issue
9eissn
0513-5796issn
1976-2437pii
61.762journal_volume
61pub_type
杂志文章abstract:PURPOSE:Several studies have demonstrated that psychiatric disorders such as anxiety, depression and panic attack are associated with syncope, especially vasovagal and unexplained syncope (US). The aim of this study was to compare the prevalence of anxiety and depression between patients with neurally mediated syncope ...
journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2013.54.3.583
更新日期:2013-05-01 00:00:00
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.1998.39.6.534
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2018.59.7.865
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journal_title:Yonsei medical journal
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更新日期:2018-06-01 00:00:00
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2016.57.6.1420
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2012.53.3.486
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journal_title:Yonsei medical journal
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doi:10.3349/ymj.2011.52.4.661
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journal_title:Yonsei medical journal
pub_type: 杂志文章
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2013.54.2.445
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pub_type: 杂志文章,随机对照试验
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2012.53.6.1113
更新日期:2012-11-01 00:00:00
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2011.52.2.301
更新日期:2011-03-01 00:00:00
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2012.53.4.742
更新日期:2012-07-01 00:00:00
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.1993.34.3.234
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2015.56.2.563
更新日期:2015-03-01 00:00:00
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.1990.31.1.33
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2008.49.5.714
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2002.43.1.37
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abstract::Genetically modified (GM) soybean (carrying the EPSPS transgene) is the most common GM food in Korea. In order to assess whether genetic modification increases the allergenic risk of soybeans, the allergenicity and IgE-reactive components of wild-type and GM soybean extracts were compared in allergic adults who had be...
journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2006.47.4.505
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journal_title:Yonsei medical journal
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journal_title:Yonsei medical journal
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doi:10.3349/ymj.2014.55.3.725
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journal_title:Yonsei medical journal
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journal_title:Yonsei medical journal
pub_type: 杂志文章
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2002.43.5.652
更新日期:2002-10-01 00:00:00
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journal_title:Yonsei medical journal
pub_type: 已发布勘误
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更新日期:2020-05-01 00:00:00
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journal_title:Yonsei medical journal
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journal_title:Yonsei medical journal
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journal_title:Yonsei medical journal
pub_type: 杂志文章
doi:10.3349/ymj.2004.45.5.944
更新日期:2004-10-31 00:00:00
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journal_title:Yonsei medical journal
pub_type: 杂志文章
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