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

Adolescent Adult Aged Biomarkers, Tumor / genetics Cohort Studies Core Binding Factors / genetics Female Gene Expression Profiling Gene Expression Regulation, Leukemic Humans Interleukin-2 Receptor alpha Subunit / genetics Karyotyping Leukemia, Myeloid, Acute / diagnosis Male Middle Aged Mutation Pilot Projects Prognosis Risk Factors Young Adult
Acute myeloid leukemia Core binding factor AML IL2RA Intermediate-risk AML NanoString Prognosis mRNA expression

Journal

Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741

Informations de publication

Date de publication:
06 06 2019
Historique:
received: 17 02 2019
accepted: 20 05 2019
entrez: 8 6 2019
pubmed: 7 6 2019
medline: 15 7 2020
Statut: epublish

Résumé

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. 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. 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). 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.

Sections du résumé

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.

Identifiants

DOI: 10.1186/s12967-019-1926-z PMID: 31171000 PMC: PMC6551869
pubmed: 31171000
doi: 10.1186/s12967-019-1926-z
pii: 10.1186/s12967-019-1926-z
pmc: PMC6551869
doi:

Substances chimiques

Biomarkers, Tumor 0
Core Binding Factors 0
IL2RA protein, human 0
Interleukin-2 Receptor alpha Subunit 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

191

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Auteurs

Wen Du (W)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Jing He (J)

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Wei Zhou (W)

Wuhan Kindstar Diagnostics, Wuhan, 430075, China.

Simin Shu (S)

Wuhan Kindstar Diagnostics, Wuhan, 430075, China.

Juan Li (J)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Wei Liu (W)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Yun Deng (Y)

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Cong Lu (C)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Shengyan Lin (S)

Department of Bioinformatics and Systems Biology, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.

Yaokun Ma (Y)

Wuhan Kindstar Diagnostics, Wuhan, 430075, China.

Yanli He (Y)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Jine Zheng (J)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Jiang Zhu (J)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Lijuan Bai (L)

Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Xiaoqing Li (X)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Junxia Yao (J)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Dan Hu (D)

Department of Cardiology and Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

Shengqing Gu (S)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Huiyu Li (H)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Anyuan Guo (A)

Department of Bioinformatics and Systems Biology, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.

Shiang Huang (S)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China.

Xiaolan Feng (X)

BC Cancer Victoria, Victoria, BC, V8R 6V5, Canada.

Dong Hu (D)

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China. dong_hu@hust.edu.cn.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. dong_hu@hust.edu.cn.
Biological Targeted Therapy Key Laboratory in Hubei, Wuhan, 430022, China. dong_hu@hust.edu.cn.
ORCID: 0000-0003-4281-9017

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › High IL2RA mRNA expression is an independent...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › High IL2RA mRNA expression is an independent...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › High IL2RA mRNA expression is an independent...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › High IL2RA mRNA expression is an independent...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › High IL2RA mRNA expression is an independent...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription CBF › High IL2RA mRNA expression is an independent...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › High IL2RA mRNA expression is an independent...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Régulation de l'expression des gènes dans la leucémie › High IL2RA mRNA expression is an independent...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › High IL2RA mRNA expression is an independent...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux cytokines › Récepteurs aux interleukines › Récepteurs à l'interleukine-2 › Sous-unité alpha du récepteur à l'interleukine-2 › High IL2RA mRNA expression is an independent...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse cytogénétique › Caryotypage › High IL2RA mRNA expression is an independent...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Leucémies › Leucémie myéloïde › Leucémie aigüe myéloïde › High IL2RA mRNA expression is an independent...
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