High IL2RA mRNA expression is an independent adverse prognostic biomarker in core binding factor and intermediate-risk acute myeloid leukemia

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dc.contributor.authorDu, Wen
dc.contributor.authorHe, Jing
dc.contributor.authorZhou, Wei
dc.contributor.authorShu, Simin
dc.contributor.authorLi, Juan
dc.contributor.authorLiu, Wei
dc.contributor.authorDeng, Yun
dc.contributor.authorLu, Cong
dc.contributor.authorLin, Shengyan
dc.contributor.authorMa, Yaokun
dc.contributor.authorHe, Yanli
dc.contributor.authorZheng, Jine
dc.contributor.authorZhu, Jiang
dc.contributor.authorBai, Lijuan
dc.contributor.authorLi, Xiaoqing
dc.contributor.authorYao, Junxia
dc.contributor.authorHu, Dan
dc.contributor.authorGu, Shengqing
dc.contributor.authorLi, Huiyu
dc.contributor.authorGuo, Anyuan
dc.contributor.authorHuang, Shiang
dc.contributor.authorFeng, Xiaolan
dc.contributor.authorHu, Dong
dc.date.accessioned2019-06-09T00:07:34Z
dc.date.available2019-06-09T00:07:34Z
dc.date.issued2019-06-06
dc.date.updated2019-06-09T00:07:33Z
dc.description.abstractAbstract Background Elevated protein expressions of CD markers such as IL2RA/CD25, CXCR4/CD184, CD34 and CD56 are associated with adverse prognosis in acute myeloid leukemia (AML). However, the prognostic value of mRNA expressions of these CD markers in AML remains unclear. Through our pilot evaluation, IL2RA mRNA expression appeared to be the best candidate as a prognostic biomarker. Therefore, the aim of this study is to characterize the prognostic value of IL2RA mRNA expression and evaluate its potential to refine prognostification in AML. Methods In a cohort of 239 newly diagnosed AML patients, IL2RA mRNA expression were measured by TaqMan realtime quantitative PCR. Morphological, cytogenetics and mutational analyses were also performed. In an intermediate-risk AML cohort with 66 patients, the mRNA expression of prognostic biomarkers (BAALC, CDKN1B, ERG, MECOM/EVI1, FLT3, ID1, IL2RA, MN1 and WT1) were quantified by NanoString technology. A TCGA cohort was analyzed to validate the prognostic value of IL2RA. For statistical analysis, Mann–Whitney U test, Fisher exact test, logistic regression, Kaplan–Meier and Cox regression analyses were used. Results In AML cohort of 239 patients, high IL2RA mRNA expression independently predicted shorter relapse free survival (RFS, p < 0.001) and overall survival (OS, p < 0.001) irrespective of age, cytogenetics, FLT3-ITD or c-KIT D816V mutational status. In core binding factor (CBF) AML, high IL2RA mRNA expression correlated with FLT3-ITD status (p = 0.023). Multivariable analyses revealed that high IL2RA expression (p = 0.002), along with c-KIT D816V status (p = 0.013) significantly predicted shorter RFS, whereas only high IL2RA mRNA expression (p = 0.014) significantly predicted shorter OS in CBF AML. In intermediate-risk AML in which multiple gene expression markers were tested by NanoString, IL2RA significantly correlated with ID1 (p = 0.006), FLT3 (p = 0.007), CDKN1B (p = 0.033) and ERG (p = 0.030) expressions. IL2RA (p < 0.001) and FLT3 (p = 0.008) expressions remained significant in predicting shorter RFS, whereas ERG (p = 0.008) and IL2RA (p = 0.044) remained significant in predicting shorter OS. Similar analyses in TCGA intermediate-risk AML showed the independent prognostic role of IL2RA in predicting event free survival (p < 0.001) and OS (p < 0.001). Conclusions High IL2RA mRNA expression is an independent and adverse prognostic factor in AML and specifically stratifies patients to worse prognosis in both CBF and intermediate-risk AML.
dc.identifier.citationJournal of Translational Medicine. 2019 Jun 06;17(1):191
dc.identifier.doihttps://doi.org/10.1186/s12967-019-1926-z
dc.identifier.urihttp://hdl.handle.net/1880/110482
dc.language.rfc3066en
dc.rights.holderThe Author(s)
dc.titleHigh IL2RA mRNA expression is an independent adverse prognostic biomarker in core binding factor and intermediate-risk acute myeloid leukemia
dc.typeJournal Article
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