Autologous T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells
Crosstalk between leukemic cells and the tumor microenvironment is of importance in chronic lymphocytic leukemia (CLL). T cells seem to sustain the survival of CLL cells by various mechanisms. The Krüppel-like family of transcription factors (KLFs) are identified as regulators of proliferation and c...
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| creator | Kokhaei, Parviz Hojjat-Farsangi, Mohammad Mozaffari, Fariba Moshfegh, Ali Pak, Fatemeh Rashidy-Pour, Ali Palma, Marzia Hansson, Lotta Österborg, Anders Mellstedt, Håkan |
| description | Crosstalk between leukemic cells and the tumor microenvironment is of importance in chronic lymphocytic leukemia (CLL). T cells seem to sustain the survival of CLL cells by various mechanisms. The Krüppel-like family of transcription factors (KLFs) are identified as regulators of proliferation and cell death. In the present study, we analyzed the expression of the wild type (WT) gene KLF6 and the oncogenic splice variant 1 (KLF6-SV1) at the mRNA level in subsets of T cells from CLL patients (n = 29), multiple myeloma patients (n = 6) and normal donors (n = 10). RNA Silencing was used for wtKLF6 and KLF6-SV1. Tumor cell apoptosis was measured. A significant overexpression of wtKLF6 and KLF6-SV1 in T cells of CLL patients compared to normal donors and myeloma patients was noted (p |
| doi_str_mv | 10.1371/journal.pone.0192839 |
| format | Article |
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T cells seem to sustain the survival of CLL cells by various mechanisms. The Krüppel-like family of transcription factors (KLFs) are identified as regulators of proliferation and cell death. In the present study, we analyzed the expression of the wild type (WT) gene KLF6 and the oncogenic splice variant 1 (KLF6-SV1) at the mRNA level in subsets of T cells from CLL patients (n = 29), multiple myeloma patients (n = 6) and normal donors (n = 10). RNA Silencing was used for wtKLF6 and KLF6-SV1. Tumor cell apoptosis was measured. A significant overexpression of wtKLF6 and KLF6-SV1 in T cells of CLL patients compared to normal donors and myeloma patients was noted (p<0.002). Western blot showed that both wtKLF6 and KLF6-SV1 were expressed in purified T cells from CLL patients. KLF6-SV1 siRNA transfection induced a significant down-regulation of KLF6-SV1 in CLL T cells, which lost the capability to sustain the growth of leukemic cells. However, no such a significant effect was seen after wtKLF6 transfection of the autologous T cells. The results suggest that KLF6-SV1 may play a role in the regulation of survival CLL cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0192839</identifier><identifier>PMID: 29432497</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alternative splicing ; Apoptosis ; Biology and Life Sciences ; Cancer research ; Cancer therapies ; Cell death ; Cell survival ; Chronic lymphocytic leukemia ; Cloning ; Crosstalk ; Development and progression ; Gastric cancer ; Gene expression ; Gene therapy ; Growth factors ; Health aspects ; Hematology ; Immunology ; Laboratories ; Leukemia ; Lymphatic leukemia ; Lymphocyte receptors ; Lymphocytes ; Lymphocytes T ; Medical prognosis ; Medical research ; Medicin och hälsovetenskap ; Medicine and Health Sciences ; Metastasis ; Multiple myeloma ; Oncology ; Pathology ; Patients ; Physiology ; Prostate ; Regulators ; Research and analysis methods ; Ribonucleic acid ; RNA ; RNA-mediated interference ; siRNA ; Stomach cancer ; Survival ; T cells ; Transcription factors ; Transfection</subject><ispartof>PloS one, 2018-02, Vol.13 (2), p.e0192839-e0192839</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Kokhaei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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T cells seem to sustain the survival of CLL cells by various mechanisms. The Krüppel-like family of transcription factors (KLFs) are identified as regulators of proliferation and cell death. In the present study, we analyzed the expression of the wild type (WT) gene KLF6 and the oncogenic splice variant 1 (KLF6-SV1) at the mRNA level in subsets of T cells from CLL patients (n = 29), multiple myeloma patients (n = 6) and normal donors (n = 10). RNA Silencing was used for wtKLF6 and KLF6-SV1. Tumor cell apoptosis was measured. A significant overexpression of wtKLF6 and KLF6-SV1 in T cells of CLL patients compared to normal donors and myeloma patients was noted (p<0.002). Western blot showed that both wtKLF6 and KLF6-SV1 were expressed in purified T cells from CLL patients. KLF6-SV1 siRNA transfection induced a significant down-regulation of KLF6-SV1 in CLL T cells, which lost the capability to sustain the growth of leukemic cells. However, no such a significant effect was seen after wtKLF6 transfection of the autologous T cells. The results suggest that KLF6-SV1 may play a role in the regulation of survival CLL cells.</description><subject>Alternative splicing</subject><subject>Apoptosis</subject><subject>Biology and Life Sciences</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cell death</subject><subject>Cell survival</subject><subject>Chronic lymphocytic leukemia</subject><subject>Cloning</subject><subject>Crosstalk</subject><subject>Development and progression</subject><subject>Gastric cancer</subject><subject>Gene expression</subject><subject>Gene therapy</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Hematology</subject><subject>Immunology</subject><subject>Laboratories</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Lymphocyte receptors</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicin 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T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells</title><author>Kokhaei, Parviz ; Hojjat-Farsangi, Mohammad ; Mozaffari, Fariba ; Moshfegh, Ali ; Pak, Fatemeh ; Rashidy-Pour, Ali ; Palma, Marzia ; Hansson, Lotta ; Österborg, Anders ; Mellstedt, Håkan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c780t-dbdf85b9ad9585902be2862e0533146b7bd5d6870113f7e88fd07ba30bce7fba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Alternative splicing</topic><topic>Apoptosis</topic><topic>Biology and Life Sciences</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Cell death</topic><topic>Cell survival</topic><topic>Chronic lymphocytic leukemia</topic><topic>Cloning</topic><topic>Crosstalk</topic><topic>Development and progression</topic><topic>Gastric cancer</topic><topic>Gene 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One</addtitle><date>2018-02-12</date><risdate>2018</risdate><volume>13</volume><issue>2</issue><spage>e0192839</spage><epage>e0192839</epage><pages>e0192839-e0192839</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Crosstalk between leukemic cells and the tumor microenvironment is of importance in chronic lymphocytic leukemia (CLL). T cells seem to sustain the survival of CLL cells by various mechanisms. The Krüppel-like family of transcription factors (KLFs) are identified as regulators of proliferation and cell death. In the present study, we analyzed the expression of the wild type (WT) gene KLF6 and the oncogenic splice variant 1 (KLF6-SV1) at the mRNA level in subsets of T cells from CLL patients (n = 29), multiple myeloma patients (n = 6) and normal donors (n = 10). RNA Silencing was used for wtKLF6 and KLF6-SV1. Tumor cell apoptosis was measured. A significant overexpression of wtKLF6 and KLF6-SV1 in T cells of CLL patients compared to normal donors and myeloma patients was noted (p<0.002). Western blot showed that both wtKLF6 and KLF6-SV1 were expressed in purified T cells from CLL patients. KLF6-SV1 siRNA transfection induced a significant down-regulation of KLF6-SV1 in CLL T cells, which lost the capability to sustain the growth of leukemic cells. However, no such a significant effect was seen after wtKLF6 transfection of the autologous T cells. The results suggest that KLF6-SV1 may play a role in the regulation of survival CLL cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29432497</pmid><doi>10.1371/journal.pone.0192839</doi><tpages>e0192839</tpages><orcidid>https://orcid.org/0000-0001-6756-0609</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2018-02, Vol.13 (2), p.e0192839-e0192839 |
| issn | 1932-6203 1932-6203 |
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| subjects | Alternative splicing Apoptosis Biology and Life Sciences Cancer research Cancer therapies Cell death Cell survival Chronic lymphocytic leukemia Cloning Crosstalk Development and progression Gastric cancer Gene expression Gene therapy Growth factors Health aspects Hematology Immunology Laboratories Leukemia Lymphatic leukemia Lymphocyte receptors Lymphocytes Lymphocytes T Medical prognosis Medical research Medicin och hälsovetenskap Medicine and Health Sciences Metastasis Multiple myeloma Oncology Pathology Patients Physiology Prostate Regulators Research and analysis methods Ribonucleic acid RNA RNA-mediated interference siRNA Stomach cancer Survival T cells Transcription factors Transfection |
| title | Autologous T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T19%3A55%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Autologous%20T%20cells%20expressing%20the%20oncogenic%20transcription%20factor%20KLF6-SV1%20prevent%20apoptosis%20of%20chronic%20lymphocytic%20leukemia%20cells&rft.jtitle=PloS%20one&rft.au=Kokhaei,%20Parviz&rft.date=2018-02-12&rft.volume=13&rft.issue=2&rft.spage=e0192839&rft.epage=e0192839&rft.pages=e0192839-e0192839&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0192839&rft_dat=%3Cgale_plos_%3EA527265121%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2001394236&rft_id=info:pmid/29432497&rft_galeid=A527265121&rft_doaj_id=oai_doaj_org_article_fcdf895cba0b43c5a53915ce617f4a25&rfr_iscdi=true |