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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| Veröffentlicht in: | International journal of molecular sciences 2023-02, Vol.24 (4), p.3860 |
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| 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. |
| doi_str_mv | 10.3390/ijms24043860 |
| format | Article |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms24043860</identifier><identifier>PMID: 36835271</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acute lymphoblastic leukemia ; Acute lymphocytic leukemia ; Antigens ; Blood ; Bone marrow ; Cancer ; Cancer therapies ; Carrier Proteins - metabolism ; CD150 antigen ; Cell surface ; Cells ; Chemotherapy ; Child ; Diagnosis ; Gene expression ; Humans ; Immunosurveillance ; Immunotherapy ; Killer Cells, Natural ; Leukemia ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - metabolism ; Lymphocytes ; Lymphocytes B ; Lymphocytes T ; Monocytes ; mRNA ; Pediatrics ; Peripheral blood mononuclear cells ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism ; Receptors, Immunologic - metabolism ; Remission (Medicine) ; RNA ; RNA sequencing ; Signaling Lymphocytic Activation Molecule Family Member 1 - metabolism ; Vincristine</subject><ispartof>International journal of molecular sciences, 2023-02, Vol.24 (4), p.3860</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-bcbb782e8721f7300bf3912d9a2329b1f63198db62f67c0f1b3cf9b47f14ecdb3</citedby><cites>FETCH-LOGICAL-c479t-bcbb782e8721f7300bf3912d9a2329b1f63198db62f67c0f1b3cf9b47f14ecdb3</cites><orcidid>0000-0001-5784-224X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9959214/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9959214/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36835271$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Powers, Sheila B</creatorcontrib><creatorcontrib>Ahmed, Nourhan G</creatorcontrib><creatorcontrib>Jose, Roslin</creatorcontrib><creatorcontrib>Brezgiel, Marissa</creatorcontrib><creatorcontrib>Aryal, Subhash</creatorcontrib><creatorcontrib>Bowman, W Paul</creatorcontrib><creatorcontrib>Mathew, Porunelloor A</creatorcontrib><creatorcontrib>Mathew, Stephen O</creatorcontrib><title>Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><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.</description><subject>Acute lymphoblastic leukemia</subject><subject>Acute lymphocytic leukemia</subject><subject>Antigens</subject><subject>Blood</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Carrier Proteins - metabolism</subject><subject>CD150 antigen</subject><subject>Cell surface</subject><subject>Cells</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Diagnosis</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Immunosurveillance</subject><subject>Immunotherapy</subject><subject>Killer Cells, Natural</subject><subject>Leukemia</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Monocytes</subject><subject>mRNA</subject><subject>Pediatrics</subject><subject>Peripheral blood mononuclear cells</subject><subject>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism</subject><subject>Receptors, Immunologic - metabolism</subject><subject>Remission (Medicine)</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>Signaling Lymphocytic Activation Molecule Family Member 1 - metabolism</subject><subject>Vincristine</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkk1v1DAQhi0Eou3CjTOyxKVI3eKvxPEFKWzLhxoKasvZsh279ZLEwU4Q_RH8Z1y2lC1CPow18_i13pkB4BlGh5QK9Mqv-0QYYrQq0QOwixkhS4RK_nDrvgP2UlojRCgpxGOwQ8uKFoTjXfDzyDtnox0mrzp4_GOMNiUfBhgcbJoLfADPm_ojPLPGjlOICa7OMVRDC8kb9juers62qqcnIys3-ZORIugH-Nm2Xk3RG1ibebKwue7Hq6A7laaca-z81fZewf26aV4-AY-c6pJ9ehsX4Mvb44vV-2Xz6d2HVd0sDeNiWmqjNa-IrTjBjlOEtKMCk1aobFBo7EqKRdXqkriSG-SwpsYJzbjDzJpW0wV4vdEdZ93b1mT7UXVyjL5X8VoG5eX9yuCv5GX4LoUoBMEsC-zfCsTwbbZpkr1PxnadGmyYkyS8QogLVIqMvvgHXYc5DtleprgoWJ4K-0tdqs5KP7iQ_zU3orLmBRaEVXlmC3D4HyqfNvfQhME6n_P3HhxsHpgYUorW3XnESN6sj9xen4w_3-7LHfxnX-gvytu9GQ</recordid><startdate>20230215</startdate><enddate>20230215</enddate><creator>Powers, Sheila B</creator><creator>Ahmed, Nourhan G</creator><creator>Jose, Roslin</creator><creator>Brezgiel, Marissa</creator><creator>Aryal, Subhash</creator><creator>Bowman, W Paul</creator><creator>Mathew, Porunelloor A</creator><creator>Mathew, Stephen O</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5784-224X</orcidid></search><sort><creationdate>20230215</creationdate><title>Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)</title><author>Powers, Sheila B ; 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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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36835271</pmid><doi>10.3390/ijms24043860</doi><orcidid>https://orcid.org/0000-0001-5784-224X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Acute lymphoblastic leukemia Acute lymphocytic leukemia Antigens Blood Bone marrow Cancer Cancer therapies Carrier Proteins - metabolism CD150 antigen Cell surface Cells Chemotherapy Child Diagnosis Gene expression Humans Immunosurveillance Immunotherapy Killer Cells, Natural Leukemia Leukocytes (mononuclear) Leukocytes, Mononuclear - metabolism Lymphocytes Lymphocytes B Lymphocytes T Monocytes mRNA Pediatrics Peripheral blood mononuclear cells Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism Receptors, Immunologic - metabolism Remission (Medicine) RNA RNA sequencing Signaling Lymphocytic Activation Molecule Family Member 1 - metabolism Vincristine |
| title | Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL) |
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