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.

Related Concept Videos

What is Gene Expression?01:42

What is Gene Expression?

Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
197.0K
What is Gene Expression?01:36

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
11.5K
Humoral Immune Responses01:36

Humoral Immune Responses

Overview
84.1K
Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
24.9K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.6K