Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)

Acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer. Most patients (85%) develop B-cell ALL; however, T-cell ALL tends to be more aggressive. We have previously identified 2B4 (SLAMF4), CS1 (SLAMF7) and LLT1 (CLEC2D) that can activate or inhibit NK cells upon the interacti...

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Main Authors: Sheila B. Powers, Nourhan G. Ahmed, Roslin Jose, Marissa Brezgiel, Subhash Aryal, W. Paul Bowman, Porunelloor A. Mathew, Stephen O. Mathew
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/4/3860
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author Sheila B. Powers
Nourhan G. Ahmed
Roslin Jose
Marissa Brezgiel
Subhash Aryal
W. Paul Bowman
Porunelloor A. Mathew
Stephen O. Mathew
author_facet Sheila B. Powers
Nourhan G. Ahmed
Roslin Jose
Marissa Brezgiel
Subhash Aryal
W. Paul Bowman
Porunelloor A. Mathew
Stephen O. Mathew
author_sort Sheila B. Powers
collection DOAJ
description Acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer. Most patients (85%) develop B-cell ALL; however, T-cell ALL tends to be more aggressive. We have previously identified 2B4 (SLAMF4), CS1 (SLAMF7) and LLT1 (CLEC2D) that can activate or inhibit NK cells upon the interaction with their ligands. In this study, the expression of 2B4, CS1, LLT1, NKp30 and NKp46 was determined. The expression profiles of these immune receptors were analyzed in the peripheral blood mononuclear cells of B-ALL and T-ALL subjects by single-cell RNA sequencing data obtained from the St. Jude PeCan data portal that showed increased expression of LLT1 in B-ALL and T-ALL subjects. Whole blood was collected from 42 pediatric ALL subjects at diagnosis and post-induction chemotherapy and 20 healthy subjects, and expression was determined at the mRNA and cell surface protein level. A significant increase in cell surface LLT1 expression in T cells, monocytes and NK cells was observed. Increased expression of CS1 and NKp46 was observed on monocytes of ALL subjects at diagnosis. A decrease of LLT1, 2B4, CS1 and NKp46 on T cells of ALL subjects was also observed post-induction chemotherapy. Furthermore, mRNA data showed altered expression of receptors in ALL subjects pre- and post-induction chemotherapy treatment. The results indicate that the differential expression of the receptors/ligand may play a role in the T-cell- and NK-cell-mediated immune surveillance of pediatric ALL.
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spelling doaj.art-0853de755d834f67bb1ddb3c96a4ef612023-11-16T21:06:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244386010.3390/ijms24043860Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)Sheila B. Powers0Nourhan G. Ahmed1Roslin Jose2Marissa Brezgiel3Subhash Aryal4W. Paul Bowman5Porunelloor A. Mathew6Stephen O. Mathew7Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USATexas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, TX 76107, USASchool of Nursing, University of Pennsylvania, Philadelphia, PA 19104, USATexas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USAAcute lymphoblastic leukemia (ALL) represents the most common pediatric cancer. Most patients (85%) develop B-cell ALL; however, T-cell ALL tends to be more aggressive. We have previously identified 2B4 (SLAMF4), CS1 (SLAMF7) and LLT1 (CLEC2D) that can activate or inhibit NK cells upon the interaction with their ligands. In this study, the expression of 2B4, CS1, LLT1, NKp30 and NKp46 was determined. The expression profiles of these immune receptors were analyzed in the peripheral blood mononuclear cells of B-ALL and T-ALL subjects by single-cell RNA sequencing data obtained from the St. Jude PeCan data portal that showed increased expression of LLT1 in B-ALL and T-ALL subjects. Whole blood was collected from 42 pediatric ALL subjects at diagnosis and post-induction chemotherapy and 20 healthy subjects, and expression was determined at the mRNA and cell surface protein level. A significant increase in cell surface LLT1 expression in T cells, monocytes and NK cells was observed. Increased expression of CS1 and NKp46 was observed on monocytes of ALL subjects at diagnosis. A decrease of LLT1, 2B4, CS1 and NKp46 on T cells of ALL subjects was also observed post-induction chemotherapy. Furthermore, mRNA data showed altered expression of receptors in ALL subjects pre- and post-induction chemotherapy treatment. The results indicate that the differential expression of the receptors/ligand may play a role in the T-cell- and NK-cell-mediated immune surveillance of pediatric ALL.https://www.mdpi.com/1422-0067/24/4/3860acute lymphoblastic leukemianatural killer cell2B4LLT1CS1NKp30
spellingShingle Sheila B. Powers
Nourhan G. Ahmed
Roslin Jose
Marissa Brezgiel
Subhash Aryal
W. Paul Bowman
Porunelloor A. Mathew
Stephen O. Mathew
Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)
International Journal of Molecular Sciences
acute lymphoblastic leukemia
natural killer cell
2B4
LLT1
CS1
NKp30
title Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)
title_full Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)
title_fullStr Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)
title_full_unstemmed Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)
title_short Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)
title_sort differential expression of llt1 slam receptors cs1 and 2b4 and ncr receptors nkp46 and nkp30 in pediatric acute lymphoblastic leukemia all
topic acute lymphoblastic leukemia
natural killer cell
2B4
LLT1
CS1
NKp30
url https://www.mdpi.com/1422-0067/24/4/3860
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