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Altered immune and treatment response gene expression signatures among povertyexposed children with B-cell acute
Amy Guillaumet-Adkins1, Elnaz Mirzaei Mehrabad2, Noori Sotudeh3
1Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA.
Insights
Children with cancer from low-income backgrounds face higher relapse risks. Poverty-linked factors in acute lymphoblastic leukemia (ALL) may drive steroid resistance and immune changes, impacting treatment outcomes.
Area of Science:
- Pediatric Oncology
- Cancer Genomics
- Immunology
Background:
- Children with cancer, particularly acute lymphoblastic leukemia (ALL), face disparities in outcomes based on socioeconomic status.
- Poverty is linked to increased cancer relapse rates and mortality in pediatric patients.
- Standardized treatment protocols do not fully mitigate the impact of poverty on childhood cancer outcomes.
Purpose of the Study:
- To investigate the molecular and cellular differences in pediatric B-acute lymphoblastic leukemia (B-ALL) associated with poverty at diagnosis.
- To identify potential mechanisms driving disparities in treatment response and disease relapse.
Main Methods:
- Single-cell RNA sequencing was employed to analyze leukemic blasts and the tumor microenvironment.
- Transcriptional signatures of poverty-exposed and non-poverty-exposed pediatric B-ALL patients were compared.
Main Results:
- Poverty-exposed pediatric B-ALL patients exhibit transcriptional signatures of steroid resistance at diagnosis.
- Increased inflammatory signatures were observed in myeloid cells from poverty-exposed children.
- Reduced effector signatures were noted in CD8+ T-cells of children with B-ALL living in poverty.
Conclusions:
- Socioeconomic status influences the molecular landscape of pediatric B-ALL at diagnosis.
- Poverty-associated transcriptional changes, including steroid resistance and immune dysregulation, may contribute to poorer outcomes.
- Further research into these mechanisms could inform risk-adapted therapeutic strategies for childhood 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 peers1,2. Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer, and children with ALL exposed to poverty are more likely to experience early relapse3. 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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