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Research article
Down-regulated FOXO1 in refractory/relapse childhood B-cell acute lymphoblastic leukemia
HUI ZHANG
The First Affiliated Hospital of Guangzhou Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8791-5753
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Refractory/relapsed acute lymphoblastic leukemia (RR-ALL) remains to be a leading cause of treatment failure and subsequent death. Forkhead box O1 (FOXO1) belongs to the forkhead family of transcription factors, its specific role in RR-ALL has not yet been determined in B-cell ALL (B-ALL). The purpose of this study was to investigate the expression and prognostic value in ALL.
Methods
RNA sequencing was applied to an ALL case with induction failure to identify the causal events. The transcription activity was examined with luciferase reporter assay. FOXO1 mRNA expression level was examined using real-time quantitative PCR. Association analysis was performed to correlate FOXO1 transcription with childhood B-ALL prognosis and relapse.
Results
In this ALL case with induction failure, we successfully identified a novel MEIS1-FOXO1 fusion gene. The transcription activity of MEIS1-FOXO1 was significantly abolished as compared to wild-type FOXO1. Low FOXO1 expression level was strongly associate with unfavorable subtype, MRD positivity and relapse.
Conclusions
FOXO1 loss of function associates with ALL high-risk stratification and relapse, which might be due to drug resistance.
Keywords
FOXO1, childhood B-cell acute lymphoblastic leukemia, relapsed/refractory
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This is a preprint. It has not completed peer review.
Research article
Down-regulated FOXO1 in refractory/relapse childhood B-cell acute lymphoblastic leukemia
HUI ZHANG
The First Affiliated Hospital of Guangzhou Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8791-5753
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 12 Mar, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Refractory/relapsed acute lymphoblastic leukemia (RR-ALL) remains to be a leading cause of treatment failure and subsequent death. Forkhead box O1 (FOXO1) belongs to the forkhead family of transcription factors, its specific role in RR-ALL has not yet been determined in B-cell ALL (B-ALL). The purpose of this study was to investigate the expression and prognostic value in ALL.
Methods
RNA sequencing was applied to an ALL case with induction failure to identify the causal events. The transcription activity was examined with luciferase reporter assay. FOXO1 mRNA expression level was examined using real-time quantitative PCR. Association analysis was performed to correlate FOXO1 transcription with childhood B-ALL prognosis and relapse.
Results
In this ALL case with induction failure, we successfully identified a novel MEIS1-FOXO1 fusion gene. The transcription activity of MEIS1-FOXO1 was significantly abolished as compared to wild-type FOXO1. Low FOXO1 expression level was strongly associate with unfavorable subtype, MRD positivity and relapse.
Conclusions
FOXO1 loss of function associates with ALL high-risk stratification and relapse, which might be due to drug resistance.
Figure 1
Figure 2
Figure 3
Figure 4