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Published on: April 14, 2010
Altered immune and treatment response gene expression signatures among poverty-exposed children with B-ALL
Amy Guillaumet-Adkins1,2, Noori Sotudeh1,3, Sayalee Potdar1
1Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Insights
Children with cancer living in poverty have a higher risk of relapse. Poverty-exposed children with acute lymphoblastic leukemia (ALL) show early signs of steroid resistance and immune changes at diagnosis.
Area of Science:
- Pediatric Oncology
- Cancer Immunology
- Socioeconomic Determinants of Health
Background:
- Children with cancer often receive standardized treatments, yet socioeconomic factors significantly impact outcomes.
- Children living in poverty face higher risks of cancer relapse and mortality compared to affluent peers.
- Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with poverty linked to increased early relapse rates.
Purpose of the Study:
- To investigate the molecular and cellular differences in pediatric B-acute lymphoblastic leukemia (B-ALL) between children exposed to poverty and their affluent counterparts at diagnosis.
- To identify potential mechanisms contributing to poorer outcomes in poverty-exposed children with B-ALL.
Main Methods:
- Single-cell RNA sequencing was employed to analyze leukemic blasts and the tumor microenvironment.
- Transcriptional signatures and immune cell profiles were compared between poverty-exposed and non-poverty-exposed pediatric B-ALL patients.
Main Results:
- Poverty-exposed children with standard-risk B-ALL exhibited transcriptional signatures indicative of steroid resistance at diagnosis.
- Increased inflammatory signatures were observed in myeloid cells, and reduced effector signatures in CD8+ T-cells of poverty-exposed B-ALL patients.
- These findings suggest distinct biological profiles associated with poverty in pediatric B-ALL.
Conclusions:
- Socioeconomic status influences the biological characteristics of pediatric B-ALL at diagnosis.
- Identifying these poverty-associated molecular and immune alterations may reveal targets for novel therapeutic strategies.
- Further research into these mechanisms could lead to risk-adapted treatments to improve outcomes for all children with ALL.
Abstract:
Children diagnosed with cancer typically receive standardized treatment regimens. Despite highly protocolized care, children living in poverty experience a greater risk of cancer relapse and higher mortality compared to their more affluent peers.1,2 Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer, and children with ALL exposed to poverty are more likely to experience early relapse.3 Using single-cell RNA sequencing to analyze leukemic blasts and their microenvironment at diagnosis we found that poverty-exposed patients with standard-risk B-ALL exhibit transcriptional signatures of steroid resistance at time of diagnosis. Additionally, we observe increased expression of inflammatory signatures in myeloid cells and reduced effector signatures in CD8+ T-cells in children with B-ALL living in poverty. Further investigation of the mechanisms underlying these associations may identify opportunities for risk-adapted therapeutic strategies to improve disease outcomes in pediatric ALL.
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