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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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TP53 alterations in relapsed childhood acute lymphoblastic leukemia
Chih-Hsiang Yu1, Wan-Ting Chang2, Shiann-Tarng Jou3
1Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Cancer Science
|November 16, 2019
Summary
TP53 gene alterations frequently emerge during relapse in childhood acute lymphoblastic leukemia (ALL). These TP53 alterations significantly worsen survival outcomes and are valuable prognostic markers in relapsed pediatric ALL patients.
Area of Science:
- Pediatric Oncology
- Cancer Genetics
- Hematology
Background:
- TP53 alterations are common acquired mutations in relapsed childhood acute lymphoblastic leukemia (ALL).
- Understanding the clinical impact of TP53 alterations in relapsed pediatric ALL is crucial for improving treatment strategies.
Purpose of the Study:
- To evaluate the clinical significance and prognostic value of TP53 alterations in Taiwanese children with relapsed ALL.
- To determine the incidence of TP53 alterations at relapse compared to diagnosis.
Main Methods:
- Analysis of diagnostic and relapsed bone marrow/peripheral blood samples from 111 children with relapsed ALL.
- Detection of TP53 mutations and copy number alterations using PCR, sequencing, and multiplex ligation-dependent probe amplification.
- Back-tracking analysis of matched diagnostic samples to identify relapse-acquired alterations.
Main Results:
- TP53 alterations were detected in 29% of B-cell ALL and 46% of T-cell ALL cases at relapse, a higher incidence than reported in Caucasian populations.
- TP53 alterations were significantly associated with lower 5-year event-free survival (EFS) and overall survival (OS) (P=.013 and P=.0002).
- TP53 alterations also predicted inferior outcomes in patients undergoing hematopoietic stem-cell transplantation post-relapse.
Conclusions:
- TP53 alterations are frequently acquired at relapse in childhood ALL and are enriched compared to diagnostic samples.
- TP53 alterations serve as significant independent prognostic markers for both survival and post-transplant outcomes in relapsed pediatric ALL.
- Targeting TP53 alterations may represent a therapeutic strategy for improving outcomes in relapsed childhood ALL.
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