Development of a poor-prognostic-mutations derived immune prognostic model for acute myeloid leukemia

Abstract Leukemia cell-intrinsic somatic mutations and cytogenetic abnormalities have been used to define risk categories in acute myeloid leukemia (AML). In addition, since the immune microenvironment might influence prognosis and somatic mutations have been demonstrated to modulate the immune micr...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Feng-Ting Dao, Jun Wang, Lu Yang, Ya-Zhen Qin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a500ffad68044c92bba0e233c3e35f84
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a500ffad68044c92bba0e233c3e35f84
record_format	dspace
spelling	oai:doaj.org-article:a500ffad68044c92bba0e233c3e35f842021-12-02T13:30:51ZDevelopment of a poor-prognostic-mutations derived immune prognostic model for acute myeloid leukemia10.1038/s41598-021-84190-02045-2322https://doaj.org/article/a500ffad68044c92bba0e233c3e35f842021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84190-0https://doaj.org/toc/2045-2322Abstract Leukemia cell-intrinsic somatic mutations and cytogenetic abnormalities have been used to define risk categories in acute myeloid leukemia (AML). In addition, since the immune microenvironment might influence prognosis and somatic mutations have been demonstrated to modulate the immune microenvironment in AML, there is need for developing and evaluating an immune prognostic model (IPM) derived from mutations associated with poor prognosis. Based on AML cases with intermediate and adverse-cytogenetic risk in the Cancer Genome Atlas (TCGA) database, 64 immune-related differentially expressed genes (DEGs) among patients with RUNX1, TP53, or ASXL1 mutations and patients without these mutations were identified. After Cox proportional hazards analysis, an IPM composed of PYCARD and PEAR1 genes was constructed. IPM defined high-risk (IPM-HR) independently predicted lower 2-year overall survival (OS) rates in both patients with intermediate and adverse-cytogenetic risks and non-M3 patients in the TCGA AML cohort. The poor prognostic impact of IPM-HR on OS was further validated by GSE71014, 37642, and 10358 downloaded from the Gene Expression Omnibus (GEO) database. Furthermore, IPM-HR was remarkably associated with higher proportions of CD8+ T cells and regulatory T cells (Tregs), lower proportions of eosinophils, and higher expression of the checkpoint molecules CTLA-4, PD-1, and LAG3 in the TCGA non-M3 AML cohort. In summary, we developed and validated an IPM derived from mutations related with poor prognosis in AML, which would provide new biomarkers for patient stratification and personalized immunotherapy.Feng-Ting DaoJun WangLu YangYa-Zhen QinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Feng-Ting Dao Jun Wang Lu Yang Ya-Zhen Qin Development of a poor-prognostic-mutations derived immune prognostic model for acute myeloid leukemia
description	Abstract Leukemia cell-intrinsic somatic mutations and cytogenetic abnormalities have been used to define risk categories in acute myeloid leukemia (AML). In addition, since the immune microenvironment might influence prognosis and somatic mutations have been demonstrated to modulate the immune microenvironment in AML, there is need for developing and evaluating an immune prognostic model (IPM) derived from mutations associated with poor prognosis. Based on AML cases with intermediate and adverse-cytogenetic risk in the Cancer Genome Atlas (TCGA) database, 64 immune-related differentially expressed genes (DEGs) among patients with RUNX1, TP53, or ASXL1 mutations and patients without these mutations were identified. After Cox proportional hazards analysis, an IPM composed of PYCARD and PEAR1 genes was constructed. IPM defined high-risk (IPM-HR) independently predicted lower 2-year overall survival (OS) rates in both patients with intermediate and adverse-cytogenetic risks and non-M3 patients in the TCGA AML cohort. The poor prognostic impact of IPM-HR on OS was further validated by GSE71014, 37642, and 10358 downloaded from the Gene Expression Omnibus (GEO) database. Furthermore, IPM-HR was remarkably associated with higher proportions of CD8+ T cells and regulatory T cells (Tregs), lower proportions of eosinophils, and higher expression of the checkpoint molecules CTLA-4, PD-1, and LAG3 in the TCGA non-M3 AML cohort. In summary, we developed and validated an IPM derived from mutations related with poor prognosis in AML, which would provide new biomarkers for patient stratification and personalized immunotherapy.
format	article
author	Feng-Ting Dao Jun Wang Lu Yang Ya-Zhen Qin
author_facet	Feng-Ting Dao Jun Wang Lu Yang Ya-Zhen Qin
author_sort	Feng-Ting Dao
title	Development of a poor-prognostic-mutations derived immune prognostic model for acute myeloid leukemia
title_short	Development of a poor-prognostic-mutations derived immune prognostic model for acute myeloid leukemia
title_full	Development of a poor-prognostic-mutations derived immune prognostic model for acute myeloid leukemia
title_fullStr	Development of a poor-prognostic-mutations derived immune prognostic model for acute myeloid leukemia
title_full_unstemmed	Development of a poor-prognostic-mutations derived immune prognostic model for acute myeloid leukemia
title_sort	development of a poor-prognostic-mutations derived immune prognostic model for acute myeloid leukemia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a500ffad68044c92bba0e233c3e35f84
work_keys_str_mv	AT fengtingdao developmentofapoorprognosticmutationsderivedimmuneprognosticmodelforacutemyeloidleukemia AT junwang developmentofapoorprognosticmutationsderivedimmuneprognosticmodelforacutemyeloidleukemia AT luyang developmentofapoorprognosticmutationsderivedimmuneprognosticmodelforacutemyeloidleukemia AT yazhenqin developmentofapoorprognosticmutationsderivedimmuneprognosticmodelforacutemyeloidleukemia
_version_	1718392932492378112

Development of a poor-prognostic-mutations derived immune prognostic model for acute myeloid leukemia

Ejemplares similares