Related Experiment Video
Updated: Jul 13, 2026
Modeling Chemotherapy Resistant Leukemia In Vitro
Published on: February 9, 2016
Gene expression prognostic of early relapse risk in low-risk B-cell acute lymphoblastic leukaemia in children
Xiaowen Gong1,2, Tianyuan Hu1,2, Qiujin Shen1,2
1State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin China.
Insights
High TIMD4 expression in children with low-risk acute lymphoblastic leukemia (ALL) indicates a higher risk of early relapse. This finding helps identify at-risk patients for better treatment strategies.
Area of Science:
- Pediatric Oncology
- Molecular Diagnostics
- Leukemia Research
Background:
- ETV6::RUNX1 fusion gene is common in childhood acute lymphoblastic leukemia (ALL), typically associated with favorable outcomes.
- A subset of children with ETV6::RUNX1-positive ALL experience early relapse, necessitating improved risk stratification.
- Identifying reliable prognostic markers for early relapse in low-risk pediatric ALL is crucial for survival.
Purpose of the Study:
- To identify novel prognostic markers for early relapse in children with low-risk ETV6::RUNX1-positive B-cell ALL.
- To investigate the association of TIMD4 expression with relapse risk in pediatric ALL.
- To validate the prognostic significance of TIMD4 expression in independent cohorts.
Main Methods:
- Somatic point mutations, genome-wide transcriptome, and single-nucleotide variants were profiled in bone marrow samples from a discovery cohort of 87 children.
- High-throughput sequencing and gene expression analysis were employed to identify molecular markers.
- Independent validation cohorts of 68 and 78 children with low-risk B-cell ALL were used to confirm findings.
Main Results:
- High TIMD4 expression (above the 85th percentile) at diagnosis was the most significant independent predictor of early relapse in the discovery cohort (HR=5.07, p=0.03).
- Validation cohorts confirmed high TIMD4 expression as a significant risk factor for early relapse in both ETV6::RUNX1-positive (HR=4.78, p=0.04) and ETV6::RUNX1-negative (HR=3.93, p=0.01) low-risk pediatric ALL.
- TIMD4 expression emerged as a consistent prognostic marker across different low-risk B-cell ALL subgroups.
Conclusions:
- Elevated TIMD4 expression at diagnosis is a potential indicator of high risk for early relapse in children with low-risk B-cell ALL.
- TIMD4 expression could serve as a valuable biomarker for refining risk stratification and guiding treatment decisions in pediatric ALL.
- Further research is warranted to elucidate the functional role of TIMD4 in ALL pathogenesis and relapse.
Abstract:
ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low-risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low-risk ETV6::RUNX1-positive B-cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome-wide transcriptome and single-nucleotide variants. We found high TIMD4 expression (> 85th-percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low-risk ETV6::RUNX1-positive B-cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ETV6::RUNX1-negative B-cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.
More Related Videos
12:58Expression of Exogenous Cytokine in Patient-derived Xenografts via Injection with a Cytokine-transduced Stromal Cell Line
Published on: May 10, 2017
09:57Comprehensive Protocol to Sample and Process Bone Marrow for Measuring Measurable Residual Disease and Leukemic Stem Cells in Acute Myeloid Leukemia
Published on: March 5, 2018
Related Concept Videos
01:49Probability Laws
01:22Bone Marrow Sampling and Transplants
The transplant begins with high doses of chemotherapy and radiation treatment, which aim to destroy the...