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Subclassification of B-acute lymphoblastic leukemia according to age, immunophenotype and microenvironment, predicts
Rubí Romo-Rodríguez1, Gabriela Zamora-Herrera1,2, Jebea A López-Blanco1
1Laboratorio de Citómica del Cáncer Infantil, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, Mexico.
Insights
A distinct ProB-ALL subtype in Mexican children over 10 years old shows a six-fold higher risk of measurable residual disease (MRD). This finding suggests a new profile for early risk stratification in acute lymphoblastic leukemia.
Area of Science:
- Pediatric Oncology
- Immunology
- Hematology
Background:
- Accurate risk stratification is crucial for disease-free survival in pediatric B-cell precursor acute lymphoblastic leukemia (B-ALL).
- Marginalized regions in Mexico face high relapse and early death rates in acute leukemias, necessitating improved diagnostic and prognostic systems.
Purpose of the Study:
- To analyze the immunophenotype, immunological context, and tumor microenvironment of pediatric acute leukemia in vulnerable Mexican children.
- To identify potential markers for risk stratification in B-ALL.
Main Methods:
- Multidimensional and integrated analysis of leukemic cell immunophenotype.
- Assessment of the immunological context and tumor microenvironment.
- Study cohort included children from vulnerable regions in Puebla, Oaxaca, and Tlaxcala, Mexico.
Main Results:
- A distinct ProB-ALL subtype was identified in children older than 10 years, associated with a six-fold increased risk of measurable residual disease (MRD).
- This subtype showed poor prognostic characteristics, including high expression of myeloid markers (MPO, CD33) and specific immunophenotypic markers, alongside a suppressive bone marrow microenvironment.
- The leukemic niche exhibited suppressive characteristics, with altered expression of key molecules and poor representation of adaptive immunity components.
Conclusions:
- A biologically distinct ProB-ALL subtype emerges in vulnerable adolescents, posing a high risk for MRD.
- The identified profile can aid in early risk stratification for pediatric B-ALL.
- Further research into environmental and lifestyle factors is crucial for detection and prevention.
Introduction:
The decisive key to disease-free survival in B-cell precursor acute lymphoblastic leukemia in children, is the combination of diagnostic timeliness and treatment efficacy, guided by accurate patient risk stratification. Implementation of standardized and high-precision diagnostic/prognostic systems is particularly important in the most marginalized geographic areas in Mexico, where high numbers of the pediatric population resides and the highest relapse and early death rates due to acute leukemias are recorded even in those cases diagnosed as standard risk.
Methods:
By using a multidimensional and integrated analysis of the immunophenotype of leukemic cells, the immunological context and the tumor microenvironment, this study aim to capture the snapshot of acute leukemia at disease debut of a cohort of Mexican children from vulnerable regions in Puebla, Oaxaca and Tlaxcala and its potential use in risk stratification.
Results And Discussion:
Our findings highlight the existence of a distinct profile of ProB-ALL in children older than 10 years, which is associated with a six-fold increase in the risk of developing measurable residual disease (MRD). Along with the absence of CD34+ seminal cells for normal hematopoiesis, this ProB-ALL subtype exhibited several characteristics related to poor prognosis, including the high expression level of myeloid lineage markers such as MPO and CD33, as well as upregulation of CD19, CD34, CD24, CD20 and nuTdT. In contrast, it showed a trend towards decreased expression of CD9, CD81, CD123, CD13, CD15 and CD21. Of note, the mesenchymal stromal cell compartment constituting their leukemic niche in the bone marrow, displayed characteristics of potential suppressive microenvironment, such as the expression of Gal9 and IDO1, and the absence of the chemokine CXCL11. Accordingly, adaptive immunity components were poorly represented. Taken together, our results suggest, for the first time, that a biologically distinct subtype of ProB-ALL emerges in vulnerable adolescents, with a high risk of developing MRD. Rigorous research on potential enhancing factors, environmental or lifestyle, is crucial for its detection and prevention. The use of the reported profile for early risk stratification is suggested.
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