# Altered Expression of NK Receptors in Racially/Ethnically Diverse and Risk-of-Relapse Pediatric Acute Lymphoblastic Leukemia Patients

**Authors:** Stephen Mathew, Roslin Jose George, Alexsis Garcia, Sheila Powers, Subhash Aryal, W. Paul Bowman

PMC · DOI: 10.3390/biomedicines13061412 · Biomedicines · 2025-06-09

## TL;DR

The study found differences in immune cell receptor expression among racially diverse and high-risk pediatric leukemia patients, which could affect treatment outcomes.

## Contribution

The study identifies race- and risk-based differences in immune receptor expression in pediatric ALL patients, offering new insights into immune surveillance mechanisms.

## Key findings

- Very high-risk and high-risk ALL patients showed increased LLT1 expression on immune cells at diagnosis.
- CS1 was overexpressed on monocytes of very-high risk ALL subjects both at diagnosis and post-chemotherapy.
- Caucasian ALL patients had higher NKp30 expression on T cells and downregulated CS1 and LLT1 post-chemotherapy compared to other ethnic groups.

## Abstract

Background/Objectives: Acute Lymphoblastic Leukemia (ALL) is a cancer that predominantly affects white blood cells within the blood and bone marrow of adults and children. Currently, ALL is one of the most prevalent malignancies in pediatric patients and is most seen among Caucasian and Hispanic descent, with lower incidence in African American children. The goal of the study was to investigate the expression of immune cell receptors in racial/ethnic populations and risk factors for relapse that could potentially influence the pediatric ALL outcomes. Methods: Twenty healthy subjects and forty-two pediatric ALL subjects were enrolled in the study and whole-blood was collected at diagnosis and post-chemotherapy, and the cell surface expression of various immune receptors, including 2B4, CS1, LLT1, Nkp30, and NKp46, was determined by flow cytometry. Results: Very high-risk and high-risk of relapse ALL subjects showed increased expression of LLT1 on NK cells, T cells, and monocytes at diagnosis compared to healthy subjects. CS1 was also significantly overexpressed on monocytes of very-high risk ALL subjects both at diagnosis and after the end of chemotherapy as compared to healthy subjects. Also, there was a significantly increased expression of NKp30 on T cells of Caucasians as compared to Hispanics and African Americans at diagnosis, and downregulation of CS1 and LLT1 on T cells of Caucasians post-induction chemotherapy. Conclusions: The altered expression of immune receptors in racial/ethnic and risk stratified groups may provide insights into the immune surveillance mediated by T cells and NK cells against pediatric ALL.

## Linked entities

- **Proteins:** CD244 (CD244 molecule), CSH1 (chorionic somatomammotropin hormone 1), CLEC2D (C-type lectin domain family 2 member D), NCR3 (natural cytotoxicity triggering receptor 3), NCR1 (natural cytotoxicity triggering receptor 1)
- **Diseases:** Acute Lymphoblastic Leukemia (MONDO:0004967), ALL (MONDO:0004967)

## Full-text entities

- **Genes:** NCR1 (natural cytotoxicity triggering receptor 1) [NCBI Gene 9437] {aka CD335, LY94, NK-p46, NKP46}, MYOZ2 (myozenin 2) [NCBI Gene 51778] {aka C4orf5, CMH16, CS-1, FATZ-2}, NCR3 (natural cytotoxicity triggering receptor 3) [NCBI Gene 259197] {aka 1C7, CD337, LY117, MALS, NKp30}, CLEC2D (C-type lectin domain family 2 member D) [NCBI Gene 29121] {aka CLAX, LLT1, OCIL}, CD244 (CD244 molecule) [NCBI Gene 51744] {aka 2B4, NAIL, NKR2B4, Nmrk, SLAMF4}
- **Diseases:** cancer (MESH:D009369), ALL (MESH:D054198)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12189698/full.md

## References

71 references — full list in the complete paper: https://tomesphere.com/paper/PMC12189698/full.md

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Source: https://tomesphere.com/paper/PMC12189698