Related Experiment Video
Updated: Jun 3, 2025
From a 2DE-Gel Spot to Protein Function: Lesson Learned From HS1 in Chronic Lymphocytic Leukemia
Published on: October 19, 2014
The Proteomics of T-Cell and Early T-Cell Precursor (ETP) Acute Lymphocytic Leukemia: Prognostic Patterns in Adult
Fieke W Hoff1, Lourdes Sriraja2, Yihua Qiu3
1Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Insights
Proteomics reveal distinct T-cell lymphocytic leukemia (T-ALL) subtypes in children and adults, aiding risk stratification. This study identifies specific protein patterns to predict outcomes in adult T-ALL and a subset of pediatric T-ALL.
Area of Science:
- Oncology
- Proteomics
- Molecular Biology
Background:
- Survival rates for T-cell lymphocytic leukemia (T-ALL) significantly differ between pediatric (>90%) and adult (~57%) patients.
- The early T-cell precursor (ETP) T-ALL subtype has a poor prognosis in adults but is less significant in pediatric T-ALL, with controversy surrounding "near"-ETP diagnosis.
- Differences in protein and RNA expression between pediatric and adult T-ALL suggest distinct disease origins and potential for age-specific prognostic markers.
Purpose of the Study:
- To compare protein and RNA expression patterns in pediatric and adult T-ALL.
- To identify prognostic subgroups within T-ALL based on molecular profiles.
- To characterize early T-cell precursor (ETP) and "near"-ETP T-ALL in both pediatric and adult populations.
Main Methods:
- Reverse phase protein array (RPPA) was used to assess 321 proteins in 361 T-ALL samples (292 pediatric, 69 adult), including 103 ETP-ALL cases.
- RNA-sequencing was performed on 81 pediatric T-ALL samples.
- MetaGalaxy analysis identified ten protein expression signatures, and Cox regression and cluster analyses were applied to assess prognostic associations.
Main Results:
- Ten recurrent protein expression patterns (signatures) were identified using MetaGalaxy analysis.
- In adults, two risk groups based on protein expression were significantly associated with overall survival (OS) and complete remission duration.
- Cluster analysis revealed three ETP-clusters associated with age; pediatric ETP-T-ALL with a pediatric-dominant profile showed shorter OS and event-free survival compared to those with an adult-like ETP profile.
Conclusions:
- Proteomic profiling is predictive of outcomes in adult T-ALL and can identify a pediatric ETP-T-ALL subset with inferior prognosis.
- Age-specific protein expression patterns support different origins for pediatric and adult T-ALL, while overlapping patterns suggest common pathogenetic mechanisms.
- Proteomics can improve risk stratification for both pediatric and adult patients diagnosed with T-ALL.
Background:
The 5-year overall survival (OS) rates of T-cell lymphocytic leukemia (T-ALL) are better for children (>90%) compared to adults (~57%). The early T-cell precursor (ETP) T-ALL subtype is prognostically unfavorable in adults, but less significant in pediatric T-ALL, and the diagnosis and prognosis of "near"-ETP is controversial. We compared protein and RNA expression patterns in pediatric and adult T-ALL to identify prognostic subgroups, and to further characterize ETP and near-ETP T-ALL in both age groups.
Methods:
Protein expression was assessed using RPPA methodology for 321 target proteins in 361 T-ALL patient samples from 292 pediatrics and 69 adults, including 103 ETP-ALL. RNA-sequencing was performed on 81 pediatric T-ALL samples.
Results:
We identified recurrent protein expression patterns that classified patients into ten protein expression signatures using the "MetaGalaxy" analysis. In adults, Cox regression analysis identified two risk-groups associated with OS (p = 0.0002) and complete remission duration (p < 0.001). Cluster analysis of adults and pediatric-ETP patients identified three ETP-clusters strongly associated with age. Pediatric ETP-patients with a pediatric-dominant expression profile were associated with a shorter OS (p = 0.04) and event-free survival (p = 0.05) compared to pediatric ETP-patients with an ETP expression profile that was also identified in adults.
Conclusion:
Our study demonstrates that proteomics are predictive of outcome in adult T-ALL and that we can identify a small subset of pediatric ETP with an inferior outcome. The observation that there are age-specific patterns supports the idea that the origin of T-ALL in most pediatric and adult patients is different, while overlapping patterns suggests that there are some with a common pathophysiology. Proteomics could enhance risk stratification in both pediatric and adults with T-ALL.
