The glutamate/aspartate transporter EAAT1 is crucial for T-cell acute lymphoblastic leukemia proliferation and survival
T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of paediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed. With the aim to identify new therapeutic...
Uloženo v:
| Vydáno v: | Haematologica (Roma) Ročník 109; číslo 11; s. 3505 - 3519 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
Italy
Fondazione Ferrata Storti
01.11.2024
Ferrata Storti Foundation |
| Témata: | |
| ISSN: | 0390-6078, 1592-8721, 1592-8721 |
| On-line přístup: | Získat plný text |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of paediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed. With the aim to identify new therapeutic targets, we combined the analysis of T-ALL gene expression and metabolism to identify the metabolic adaptations that T-ALL cells exhibit. We found that glutamine uptake is essential for T-ALL proliferation. Isotope tracing experiments showed that glutamine fuels aspartate synthesis through the TCA cycle and that glutamine and glutamine-derived aspartate together supply three nitrogen atoms in purines and all but one atom in pyrimidine rings. We show that the glutamate-aspartate transporter EAAT1 (SLC1A3), which is normally expressed in the central nervous system, is crucial for glutamine conversion to aspartate and nucleotides and that T-ALL cell proliferation depends on EAAT1 function. Through this work, we identify EAAT1 as a novel therapeutic target for T-ALL treatment. |
|---|---|
| AbstractList | T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of pediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed. With the aim to identify new therapeutic targets, we combined the analysis of T-ALL gene expression and metabolism to identify the metabolic adaptations that T-ALL cells exhibit. We found that glutamine uptake is essential for T-ALL proliferation. Isotope tracing experiments showed that glutamine fuels aspartate synthesis through the tricarboxylic acid cycle and that glutamine and glutamine-derived aspartate together supply three nitrogen atoms in purines and all but one atom in pyrimidine rings. We show that the glutamate-aspartate transporter EAAT1 (SLC1A3), which is normally expressed in the central nervous system, is crucial for glutamine conversion to aspartate and nucleotides and that T-ALL cell proliferation depends on EAAT1 function. Through this work, we identify EAAT1 as a novel therapeutic target for T-ALL treatment. T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of pediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed. With the aim to identify new therapeutic targets, we combined the analysis of T-ALL gene expression and metabolism to identify the metabolic adaptations that T-ALL cells exhibit. We found that glutamine uptake is essential for T-ALL proliferation. Isotope tracing experiments showed that glutamine fuels aspartate synthesis through the tricarboxylic acid cycle and that glutamine and glutamine-derived aspartate together supply three nitrogen atoms in purines and all but one atom in pyrimidine rings. We show that the glutamate-aspartate transporter EAAT1 (SLC1A3), which is normally expressed in the central nervous system, is crucial for glutamine conversion to aspartate and nucleotides and that T-ALL cell proliferation depends on EAAT1 function. Through this work, we identify EAAT1 as a novel therapeutic target for T-ALL treatment.T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of pediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed. With the aim to identify new therapeutic targets, we combined the analysis of T-ALL gene expression and metabolism to identify the metabolic adaptations that T-ALL cells exhibit. We found that glutamine uptake is essential for T-ALL proliferation. Isotope tracing experiments showed that glutamine fuels aspartate synthesis through the tricarboxylic acid cycle and that glutamine and glutamine-derived aspartate together supply three nitrogen atoms in purines and all but one atom in pyrimidine rings. We show that the glutamate-aspartate transporter EAAT1 (SLC1A3), which is normally expressed in the central nervous system, is crucial for glutamine conversion to aspartate and nucleotides and that T-ALL cell proliferation depends on EAAT1 function. Through this work, we identify EAAT1 as a novel therapeutic target for T-ALL treatment. T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of paediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed. With the aim to identify new therapeutic targets, we combined the analysis of T-ALL gene expression and metabolism to identify the metabolic adaptations that T-ALL cells exhibit. We found that glutamine uptake is essential for T-ALL proliferation. Isotope tracing experiments showed that glutamine fuels aspartate synthesis through the TCA cycle and that glutamine and glutamine-derived aspartate together supply three nitrogen atoms in purines and all but one atom in pyrimidine rings. We show that the glutamate-aspartate transporter EAAT1 (SLC1A3), which is normally expressed in the central nervous system, is crucial for glutamine conversion to aspartate and nucleotides and that T-ALL cell proliferation depends on EAAT1 function. Through this work, we identify EAAT1 as a novel therapeutic target for T-ALL treatment. |
| Author | Sarkar, Sovan Dimeloe, Sarah Perry, Tracey A. Reed, Michelle A.C. Pratt, Guy Stanulović, Vesna S. Al Omair, Shorog Bishop, Emma L. Roberts, Jennie Gudgeon, Nancy Ludwig, Christian Hoogenkamp, Maarten Potluri, Sandeep Günther, Ulrich L. Taghon, Tom Roels, Juliette Fulton-Ward, Taylor |
| AuthorAffiliation | 4 Center for Clinical Hematology, Queen Elizabeth Hospital Birmingham, Birmingham, UK 1 Institute of Cancer and Genomic Sciences, University of Birmingham , Birmingham, UK 5 Institute of Metabolism and Systems Research, University of Birmingham , Birmingham, UK 2 Institute of Immunology and Immunotherapy, University of Birmingham , Birmingham, UK 3 Department of Diagnostic Sciences, Ghent University , Ghent, Belgium |
| AuthorAffiliation_xml | – name: 2 Institute of Immunology and Immunotherapy, University of Birmingham , Birmingham, UK – name: 4 Center for Clinical Hematology, Queen Elizabeth Hospital Birmingham, Birmingham, UK – name: 5 Institute of Metabolism and Systems Research, University of Birmingham , Birmingham, UK – name: 1 Institute of Cancer and Genomic Sciences, University of Birmingham , Birmingham, UK – name: 3 Department of Diagnostic Sciences, Ghent University , Ghent, Belgium |
| Author_xml | – sequence: 1 givenname: Vesna S. surname: Stanulović fullname: Stanulović, Vesna S. – sequence: 2 givenname: Shorog surname: Al Omair fullname: Al Omair, Shorog – sequence: 3 givenname: Michelle A.C. surname: Reed fullname: Reed, Michelle A.C. – sequence: 4 givenname: Jennie surname: Roberts fullname: Roberts, Jennie – sequence: 5 givenname: Sandeep surname: Potluri fullname: Potluri, Sandeep – sequence: 6 givenname: Taylor surname: Fulton-Ward fullname: Fulton-Ward, Taylor – sequence: 7 givenname: Nancy surname: Gudgeon fullname: Gudgeon, Nancy – sequence: 8 givenname: Emma L. surname: Bishop fullname: Bishop, Emma L. – sequence: 9 givenname: Juliette surname: Roels fullname: Roels, Juliette – sequence: 10 givenname: Tracey A. surname: Perry fullname: Perry, Tracey A. – sequence: 11 givenname: Sovan surname: Sarkar fullname: Sarkar, Sovan – sequence: 12 givenname: Guy surname: Pratt fullname: Pratt, Guy – sequence: 13 givenname: Tom surname: Taghon fullname: Taghon, Tom – sequence: 14 givenname: Sarah surname: Dimeloe fullname: Dimeloe, Sarah – sequence: 15 givenname: Ulrich L. surname: Günther fullname: Günther, Ulrich L. – sequence: 16 givenname: Christian surname: Ludwig fullname: Ludwig, Christian – sequence: 17 givenname: Maarten surname: Hoogenkamp fullname: Hoogenkamp, Maarten |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38813748$$D View this record in MEDLINE/PubMed |
| BookMark | eNpVkk1v1DAQhiNURD_gHyDkI5ds_Rk7J7SqClSqxGU5W7POeNfFiYOdLOq_J8u2FT15ZL96ZvzOe1mdDWnAqvrI6EoILq_3gD1MKa445WLFjZCavakumGp5bTRnZ9UFFS2tG6rNeXVZygOlnLatfledC2OY0NJcVH82eyS7OE-wwPAaygh5WioyZRjKmPKEmdyu1xtGQiEuzy5AJD5lsqkdxkjAzYs6PvbjPm0jlCk4EnH-hX0AMuYUg8cMU0gDgaEjZc6HcID4vnrrIRb88HReVT-_3m5uvtf3P77d3azvaye5nGr0AriSrNVeK-oM1dLp1hmvmMcGFQhJvUDZ8E4rKTTttsCU7lQnhEGjxFV1d-J2CR7smEMP-dEmCPbfRco7u3w4uIjWtIjKa7FF2kne8Za2zjcSBZVCKdAL68uJNc7bHjuHw2JSfAV9_TKEvd2lg2VMCd4YsxA-PxFy-j1jmWwfytFGGDDNxQracCUoZcfBP_3f7KXL8-oWgTwJXE6lZPQvEkbtMSH2OSH2mBB7Soj4CwVNsnw |
| ContentType | Journal Article |
| Copyright | Copyright© 2024 Ferrata Storti Foundation |
| Copyright_xml | – notice: Copyright© 2024 Ferrata Storti Foundation |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM DOA |
| DOI | 10.3324/haematol.2023.283471 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic CrossRef |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine Anatomy & Physiology |
| EISSN | 1592-8721 |
| EndPage | 3519 |
| ExternalDocumentID | oai_doaj_org_article_89ee5f73be0d42d2909cf64e304355a7 PMC11532688 38813748 10_3324_haematol_2023_283471 |
| Genre | Journal Article |
| GrantInformation_xml | – fundername: Wellcome Trust |
| GroupedDBID | --- 29I 2WC 53G 5GY 5RE 5VS AAFWJ AAYXX ADBBV AENEX AFPKN ALMA_UNASSIGNED_HOLDINGS AOIJS BAWUL BCNDV BTFSW CITATION CS3 DIK E3Z EBS EJD F5P FRP GROUPED_DOAJ H13 HYE KQ8 OK1 OVT P2P RHI RNS RPM SJN TFS TR2 W8F WOQ WOW CGR CUY CVF ECM EIF NPM 7X8 5PM |
| ID | FETCH-LOGICAL-c424t-ef3a254197f750c8074c79c8f51fe6e5a340f3e462d754370dba157d5d338e853 |
| IEDL.DBID | DOA |
| ISICitedReferencesCount | 2 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001371211100011&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0390-6078 1592-8721 |
| IngestDate | Fri Oct 03 12:39:02 EDT 2025 Tue Sep 30 17:07:15 EDT 2025 Thu Oct 02 05:22:19 EDT 2025 Mon Jul 21 06:05:18 EDT 2025 Sat Nov 29 06:33:11 EST 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 11 |
| Language | English |
| License | http://creativecommons.org/licenses/by-nc/4.0 This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c424t-ef3a254197f750c8074c79c8f51fe6e5a340f3e462d754370dba157d5d338e853 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Disclosures No conflicts of interest to disclose. |
| OpenAccessLink | https://doaj.org/article/89ee5f73be0d42d2909cf64e304355a7 |
| PMID | 38813748 |
| PQID | 3062530015 |
| PQPubID | 23479 |
| PageCount | 15 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_89ee5f73be0d42d2909cf64e304355a7 pubmedcentral_primary_oai_pubmedcentral_nih_gov_11532688 proquest_miscellaneous_3062530015 pubmed_primary_38813748 crossref_primary_10_3324_haematol_2023_283471 |
| PublicationCentury | 2000 |
| PublicationDate | 2024-11-01 |
| PublicationDateYYYYMMDD | 2024-11-01 |
| PublicationDate_xml | – month: 11 year: 2024 text: 2024-11-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | Italy |
| PublicationPlace_xml | – name: Italy |
| PublicationTitle | Haematologica (Roma) |
| PublicationTitleAlternate | Haematologica |
| PublicationYear | 2024 |
| Publisher | Fondazione Ferrata Storti Ferrata Storti Foundation |
| Publisher_xml | – name: Fondazione Ferrata Storti – name: Ferrata Storti Foundation |
| SSID | ssj0020997 |
| Score | 2.4565616 |
| Snippet | T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of paediatric and 50% of adult T-ALL patients have refractory... T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of pediatric and 50% of adult T-ALL patients have refractory... |
| SourceID | doaj pubmedcentral proquest pubmed crossref |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database |
| StartPage | 3505 |
| SubjectTerms | Acute Lymphoblastic Leukemia Aspartic Acid - metabolism Cell Line, Tumor Cell Proliferation Cell Survival Excitatory Amino Acid Transporter 1 - genetics Excitatory Amino Acid Transporter 1 - metabolism Glutamine - metabolism Humans Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology |
| Title | The glutamate/aspartate transporter EAAT1 is crucial for T-cell acute lymphoblastic leukemia proliferation and survival |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/38813748 https://www.proquest.com/docview/3062530015 https://pubmed.ncbi.nlm.nih.gov/PMC11532688 https://doaj.org/article/89ee5f73be0d42d2909cf64e304355a7 |
| Volume | 109 |
| WOSCitedRecordID | wos001371211100011&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals customDbUrl: eissn: 1592-8721 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0020997 issn: 0390-6078 databaseCode: DOA dateStart: 19940101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3Pb9MwFH6CCSEuiG3AssFkJMTN1Imd2j4WtIkLE4ci9RY59jOr2NKpbZj23-85SasVIXHZNYliy99nv-_5x2eAj4UIOQlzxVUtAldYRF7XpeaW1Ik0rkRRu-6yCX1xYWYz--PBVV9pT1hvD9w33MhYxDJqWaMIqgiFFdbHsUJKwylUuu4cOf13k0wNqVY6D9qtH1hKjigK9ofmJKmH0aVLZqiLtOxQyM8UXZXOd4JS593_L8H5977JB4Ho_BW8HBQkm_Q134cn2BzA4aSh0q7v2CfW7ensJssP4Pn3Yen8EG6JEOwX8cxRvXDkaCRJy_DI1lt78yU7m0ymOZuvmCfIiZmMJC2b8jS7z5xv6eurO4J_UZPmpuLZFba_8Xru2E26_CdiTyfmmsBWLQ1CROPX8PP8bPr1Gx9uXeBeFWrNMUpHWWNudSQ14ZNZjtfWm1jmEcdYOqlElKjGRdClklqE2uWlDmWgbBcp-r-BvWbR4BEwUTing7MEeRJqxong3TgKr5Q1PtgM-KbZq5veXKOipCTBVG1gqhJMVQ9TBl8SNttvkzV294AIUw2Eqf5HmAw-bJCtqCulFnQNLtpVRdlTUcqkIjN42yO9LUoakyenngzMDgd26rL7pplfdnbdpLlJIxtz_Bi1P4EX1CCqPw35DvbWyxbfwzP_Zz1fLU_hqZ6Z064r3AMXOA3s |
| linkProvider | Directory of Open Access Journals |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+glutamate%2Faspartate+transporter+EAAT1+is+crucial+for+T-cell+acute+lymphoblastic+leukemia+proliferation+and+survival&rft.jtitle=Haematologica+%28Roma%29&rft.au=Stanulovi%C4%87%2C+Vesna+S.&rft.au=Al+Omair%2C+Shorog&rft.au=Reed%2C+Michelle+A.C.&rft.au=Roberts%2C+Jennie&rft.date=2024-11-01&rft.pub=Fondazione+Ferrata+Storti&rft.issn=0390-6078&rft.eissn=1592-8721&rft.volume=109&rft.issue=11&rft.spage=3505&rft.epage=3519&rft_id=info:doi/10.3324%2Fhaematol.2023.283471&rft_id=info%3Apmid%2F38813748&rft.externalDocID=PMC11532688 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0390-6078&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0390-6078&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0390-6078&client=summon |