MN1, FOXP1 and hsa-miR-181a-5p as prognostic markers in acute myeloid leukemia patients treated with intensive induction chemotherapy and autologous stem cell transplantation.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Biomarkers, Tumor
Female
Forkhead Transcription Factors
/ genetics
Gene Expression Regulation, Neoplastic
Hematopoietic Stem Cell Transplantation
Humans
Induction Chemotherapy
Leukemia, Myeloid, Acute
/ genetics
Male
MicroRNAs
/ genetics
Middle Aged
Models, Biological
Mutation
Nucleophosmin
Prognosis
Repressor Proteins
/ genetics
Retrospective Studies
Trans-Activators
/ genetics
Transplantation, Autologous
Treatment Outcome
Tumor Suppressor Proteins
/ genetics
Young Adult
Acute myeloid leukemia (AML)
Autologous stem cell transplantation (auto-SCT)
Leukemic stem cell (LSC)
Stem cell surface marker CD34
Transcription co-regulator Meningioma-1 (MN1)
Journal
Leukemia research
ISSN: 1873-5835
Titre abrégé: Leuk Res
Pays: England
ID NLM: 7706787
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
11
10
2019
revised:
11
12
2019
accepted:
01
01
2020
pubmed:
14
1
2020
medline:
15
9
2020
entrez:
14
1
2020
Statut:
ppublish
Résumé
The meningioma-1 (MN1) gene is expressed in hematopoietic CD34+ cells and down-regulated during myeloid differentiation. MN1 overexpression has been linked to shorter overall and disease free survival in AML patients treated with intensive induction chemotherapy. MN1 overexpression may still be an adverse prognostic marker in AML patients treated with autologous stem cell transplant (auto-SCT) after intensive induction chemotherapy. We retrospectively analysed 54 peripheral blood mononuclear cell (PBMC) samples of AML patients who received auto-SCT at remission (CR1) after intensive induction chemotherapy. MN1 and putative MN1-associated mRNAs, as well as MN1-associated micro-RNAs were assessed at diagnosis in peripheral blood mononuclear cells using Taqman gene expression assays. AML patients with elevated MN1 or FoxP1 gene expression at diagnosis had a significantly shorter progression-free and overall survival after intensive induction chemo-therapy and auto-SCT. The presence of the favourable risk NPM1 mutation associated with reduced MN1 gene expression. In contrast to MN1 and FOXP1, elevated expression of the putative tumor suppressive micro-RNA hsa-miR-181a-5p was predictive for positive outcome. Correlation analysis of MN1 with myeloid gene expression levels revealed association of MN1 and BMI-1, CD34, FOXP1 and MDM2 expression. Analysis of non-coding RNAs revealed an inverse correlation of MN1 with hsa-miR-20a-5p and hsa-miR-181b-5p expression. MN1, FOXP1 and hsa-miR-181a-5p are prognostic markers in AML patients treated with intensive induction chemotherapy and auto-SCT. While MDM2 is a validated therapeutic target, the transcription factors MN1 and FOXP1, and the chromatin modulator BMI-1 are potential therapeutic targets in the treatment of AML. The tumor suppressor hsa-miR-181a-5p may be a candidate miRNA mimic for therapeutic use.
Sections du résumé
BACKGROUND
The meningioma-1 (MN1) gene is expressed in hematopoietic CD34+ cells and down-regulated during myeloid differentiation. MN1 overexpression has been linked to shorter overall and disease free survival in AML patients treated with intensive induction chemotherapy. MN1 overexpression may still be an adverse prognostic marker in AML patients treated with autologous stem cell transplant (auto-SCT) after intensive induction chemotherapy.
METHODS
We retrospectively analysed 54 peripheral blood mononuclear cell (PBMC) samples of AML patients who received auto-SCT at remission (CR1) after intensive induction chemotherapy. MN1 and putative MN1-associated mRNAs, as well as MN1-associated micro-RNAs were assessed at diagnosis in peripheral blood mononuclear cells using Taqman gene expression assays.
RESULTS
AML patients with elevated MN1 or FoxP1 gene expression at diagnosis had a significantly shorter progression-free and overall survival after intensive induction chemo-therapy and auto-SCT. The presence of the favourable risk NPM1 mutation associated with reduced MN1 gene expression. In contrast to MN1 and FOXP1, elevated expression of the putative tumor suppressive micro-RNA hsa-miR-181a-5p was predictive for positive outcome. Correlation analysis of MN1 with myeloid gene expression levels revealed association of MN1 and BMI-1, CD34, FOXP1 and MDM2 expression. Analysis of non-coding RNAs revealed an inverse correlation of MN1 with hsa-miR-20a-5p and hsa-miR-181b-5p expression.
CONCLUSIONS
MN1, FOXP1 and hsa-miR-181a-5p are prognostic markers in AML patients treated with intensive induction chemotherapy and auto-SCT. While MDM2 is a validated therapeutic target, the transcription factors MN1 and FOXP1, and the chromatin modulator BMI-1 are potential therapeutic targets in the treatment of AML. The tumor suppressor hsa-miR-181a-5p may be a candidate miRNA mimic for therapeutic use.
Identifiants
pubmed: 31927137
pii: S0145-2126(20)30001-1
doi: 10.1016/j.leukres.2020.106296
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
FOXP1 protein, human
0
Forkhead Transcription Factors
0
MIrn181 microRNA, human
0
MN1 protein, human
0
MicroRNAs
0
NPM1 protein, human
0
Repressor Proteins
0
Trans-Activators
0
Tumor Suppressor Proteins
0
Nucleophosmin
117896-08-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106296Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no potential conflicts of interest.