Inhibition of casein kinase 2 induces cell death in tyrosine kinase inhibitor resistant chronic myelogenous leukemia cells
Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the BCR-ABL oncogene. Despite the high performance of treatment with tyrosine kinase inhibitors (TKI), about 30% of patients develop resistance to the therapy. To improve the outcomes, identification of new targets o...
Gespeichert in:
| Veröffentlicht in: | PloS one 2023-05, Vol.18 (5), p.e0284876-e0284876 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0284876 |
|---|---|
| container_issue | 5 |
| container_start_page | e0284876 |
| container_title | PloS one |
| container_volume | 18 |
| creator | Mitrovský, Ondřej Myslivcová, Denisa Macháčková-Lopotová, Tereza Obr, Adam Čermáková, Kamila Ransdorfová, Šárka Březinová, Jana Klamová, Hana Žáčková, Markéta |
| description | Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the BCR-ABL oncogene. Despite the high performance of treatment with tyrosine kinase inhibitors (TKI), about 30% of patients develop resistance to the therapy. To improve the outcomes, identification of new targets of treatment is needed. Here, we explored the Casein Kinase 2 (CK2) as a potential target for CML therapy. Previously, we detected increased phosphorylation of HSP90β Serine 226 in patients non-responding to TKIs imatinib and dasatinib. This site is known to be phosphorylated by CK2, which was also linked to CML resistance to imatinib. In the present work, we established six novel imatinib- and dasatinib-resistant CML cell lines, all of which had increased CK2 activation. A CK2 inhibitor, CX-4945, induced cell death of CML cells in both parental and resistant cell lines. In some cases, CK2 inhibition also potentiated the effects of TKI on the cell metabolic activity. No effects of CK2 inhibition were observed in normal mononuclear blood cells from healthy donors and BCR-ABL negative HL60 cell line. Our data indicate that CK2 kinase supports CML cell viability even in cells with different mechanisms of resistance to TKI, and thus represents a potential target for treatment. |
| doi_str_mv | 10.1371/journal.pone.0284876 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2809480424</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A748058752</galeid><doaj_id>oai_doaj_org_article_bd7d2e3660b04a6fbabf4e0148eba6b9</doaj_id><sourcerecordid>A748058752</sourcerecordid><originalsourceid>FETCH-LOGICAL-c693t-abca32fab9f1c2f929076d76ccfbe0614418a1634ca91862e0757e9b3ca131173</originalsourceid><addsrcrecordid>eNqNk9uO0zAQhiMEYpfCGyCwhITgosWnOMkVWq04VFppJU63lu1MGu-mdrETRHl63DZdNWgvUC5ijb_5bf8zk2XPCV4QVpB3N34ITnWLjXewwLTkZSEeZOekYnQuKGYPT9Zn2ZMYbzDOWSnE4-ws5XNCCT3P_ixda7XtrXfIN8ioCNahW-vSAlFkXT0YiMhA16EaVN-mEOq3wUfr4MjZg4YPKEC0sVeuR6YN3lmD1lvo_AqcHyLqYLiFtVV7ufg0e9SoLsKz8T_Lvn_88O3y8_zq-tPy8uJqbkTF-rnSRjHaKF01xNCmohUuRF0IYxoNWBDOSamIYNyoipSCAi7yAirNjCKMkILNspcH3U3noxxti5KWuOIl5pQnYnkgaq9u5CbYtQpb6ZWV-4APK6lCb00HUtdFTYEJgTXmSjRa6YYDJrwErYSuktb78bRBr6E24PqguonodMfZVq78L0kwySuyv82bUSH4nwPEXq5t3DmmHCQX9xfPOS1SNWfZq3_Q-583UiuVXmBd49PBZicqL4rE5GWR00Qt7qHSV6eSmdRkjU3xScLbSUJievjdr9QQo1x-_fL_7PWPKfv6hG1BdX0bfTfsejROQX4ATWrHGKC5c5lguZuRoxtyNyNynJGU9uK0QndJx6FgfwF4CQ4W</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2809480424</pqid></control><display><type>article</type><title>Inhibition of casein kinase 2 induces cell death in tyrosine kinase inhibitor resistant chronic myelogenous leukemia cells</title><source>PLoS (Open access)</source><source>PubMed Central (Open access)</source><source>MEDLINE</source><source>Full-Text Journals in Chemistry (Open access)</source><source>Directory of Open Access Journals</source><source>EZB Electronic Journals Library</source><creator>Mitrovský, Ondřej ; Myslivcová, Denisa ; Macháčková-Lopotová, Tereza ; Obr, Adam ; Čermáková, Kamila ; Ransdorfová, Šárka ; Březinová, Jana ; Klamová, Hana ; Žáčková, Markéta</creator><contributor>Kancha, Rama Krishna</contributor><creatorcontrib>Mitrovský, Ondřej ; Myslivcová, Denisa ; Macháčková-Lopotová, Tereza ; Obr, Adam ; Čermáková, Kamila ; Ransdorfová, Šárka ; Březinová, Jana ; Klamová, Hana ; Žáčková, Markéta ; Kancha, Rama Krishna</creatorcontrib><description>Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the BCR-ABL oncogene. Despite the high performance of treatment with tyrosine kinase inhibitors (TKI), about 30% of patients develop resistance to the therapy. To improve the outcomes, identification of new targets of treatment is needed. Here, we explored the Casein Kinase 2 (CK2) as a potential target for CML therapy. Previously, we detected increased phosphorylation of HSP90β Serine 226 in patients non-responding to TKIs imatinib and dasatinib. This site is known to be phosphorylated by CK2, which was also linked to CML resistance to imatinib. In the present work, we established six novel imatinib- and dasatinib-resistant CML cell lines, all of which had increased CK2 activation. A CK2 inhibitor, CX-4945, induced cell death of CML cells in both parental and resistant cell lines. In some cases, CK2 inhibition also potentiated the effects of TKI on the cell metabolic activity. No effects of CK2 inhibition were observed in normal mononuclear blood cells from healthy donors and BCR-ABL negative HL60 cell line. Our data indicate that CK2 kinase supports CML cell viability even in cells with different mechanisms of resistance to TKI, and thus represents a potential target for treatment.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0284876</identifier><identifier>PMID: 37141212</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abl protein ; Antibodies ; Apoptosis ; BCR protein ; Biochemistry ; Biology and Life Sciences ; Blood cells ; Cancer therapies ; Care and treatment ; Casein ; Casein Kinase II ; Cell Death ; Cell growth ; Cell viability ; Chronic myeloid leukemia ; Dasatinib - pharmacology ; Drug Resistance, Neoplasm ; Enzyme inhibitors ; Experiments ; Fusion protein ; Fusion Proteins, bcr-abl - metabolism ; Health aspects ; Heat shock proteins ; Humans ; Imatinib ; Imatinib Mesylate - pharmacology ; Kinases ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy ; Leukocytes ; Medicine and Health Sciences ; Mutation ; Myeloid leukemia ; Myeloproliferative diseases ; Nilotinib ; Patient outcomes ; Patients ; Phenols ; Phosphorylation ; Protein Kinase Inhibitors - pharmacology ; Protein-tyrosine kinase ; Proteins ; Research and Analysis Methods ; Tyrosine ; Tyrosine Kinase Inhibitors</subject><ispartof>PloS one, 2023-05, Vol.18 (5), p.e0284876-e0284876</ispartof><rights>Copyright: © 2023 Mitrovský et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Mitrovský 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. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Mitrovský et al 2023 Mitrovský et al</rights><rights>2023 Mitrovský 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. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c693t-abca32fab9f1c2f929076d76ccfbe0614418a1634ca91862e0757e9b3ca131173</citedby><cites>FETCH-LOGICAL-c693t-abca32fab9f1c2f929076d76ccfbe0614418a1634ca91862e0757e9b3ca131173</cites><orcidid>0000-0003-0057-076X</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/PMC10159124/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10159124/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2106,2932,23875,27933,27934,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37141212$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kancha, Rama Krishna</contributor><creatorcontrib>Mitrovský, Ondřej</creatorcontrib><creatorcontrib>Myslivcová, Denisa</creatorcontrib><creatorcontrib>Macháčková-Lopotová, Tereza</creatorcontrib><creatorcontrib>Obr, Adam</creatorcontrib><creatorcontrib>Čermáková, Kamila</creatorcontrib><creatorcontrib>Ransdorfová, Šárka</creatorcontrib><creatorcontrib>Březinová, Jana</creatorcontrib><creatorcontrib>Klamová, Hana</creatorcontrib><creatorcontrib>Žáčková, Markéta</creatorcontrib><title>Inhibition of casein kinase 2 induces cell death in tyrosine kinase inhibitor resistant chronic myelogenous leukemia cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the BCR-ABL oncogene. Despite the high performance of treatment with tyrosine kinase inhibitors (TKI), about 30% of patients develop resistance to the therapy. To improve the outcomes, identification of new targets of treatment is needed. Here, we explored the Casein Kinase 2 (CK2) as a potential target for CML therapy. Previously, we detected increased phosphorylation of HSP90β Serine 226 in patients non-responding to TKIs imatinib and dasatinib. This site is known to be phosphorylated by CK2, which was also linked to CML resistance to imatinib. In the present work, we established six novel imatinib- and dasatinib-resistant CML cell lines, all of which had increased CK2 activation. A CK2 inhibitor, CX-4945, induced cell death of CML cells in both parental and resistant cell lines. In some cases, CK2 inhibition also potentiated the effects of TKI on the cell metabolic activity. No effects of CK2 inhibition were observed in normal mononuclear blood cells from healthy donors and BCR-ABL negative HL60 cell line. Our data indicate that CK2 kinase supports CML cell viability even in cells with different mechanisms of resistance to TKI, and thus represents a potential target for treatment.</description><subject>Abl protein</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>BCR protein</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Blood cells</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Casein</subject><subject>Casein Kinase II</subject><subject>Cell Death</subject><subject>Cell growth</subject><subject>Cell viability</subject><subject>Chronic myeloid leukemia</subject><subject>Dasatinib - pharmacology</subject><subject>Drug Resistance, Neoplasm</subject><subject>Enzyme inhibitors</subject><subject>Experiments</subject><subject>Fusion protein</subject><subject>Fusion Proteins, bcr-abl - metabolism</subject><subject>Health aspects</subject><subject>Heat shock proteins</subject><subject>Humans</subject><subject>Imatinib</subject><subject>Imatinib Mesylate - pharmacology</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy</subject><subject>Leukocytes</subject><subject>Medicine and Health Sciences</subject><subject>Mutation</subject><subject>Myeloid leukemia</subject><subject>Myeloproliferative diseases</subject><subject>Nilotinib</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Phenols</subject><subject>Phosphorylation</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein-tyrosine kinase</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Tyrosine</subject><subject>Tyrosine Kinase Inhibitors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9uO0zAQhiMEYpfCGyCwhITgosWnOMkVWq04VFppJU63lu1MGu-mdrETRHl63DZdNWgvUC5ijb_5bf8zk2XPCV4QVpB3N34ITnWLjXewwLTkZSEeZOekYnQuKGYPT9Zn2ZMYbzDOWSnE4-ws5XNCCT3P_ixda7XtrXfIN8ioCNahW-vSAlFkXT0YiMhA16EaVN-mEOq3wUfr4MjZg4YPKEC0sVeuR6YN3lmD1lvo_AqcHyLqYLiFtVV7ufg0e9SoLsKz8T_Lvn_88O3y8_zq-tPy8uJqbkTF-rnSRjHaKF01xNCmohUuRF0IYxoNWBDOSamIYNyoipSCAi7yAirNjCKMkILNspcH3U3noxxti5KWuOIl5pQnYnkgaq9u5CbYtQpb6ZWV-4APK6lCb00HUtdFTYEJgTXmSjRa6YYDJrwErYSuktb78bRBr6E24PqguonodMfZVq78L0kwySuyv82bUSH4nwPEXq5t3DmmHCQX9xfPOS1SNWfZq3_Q-583UiuVXmBd49PBZicqL4rE5GWR00Qt7qHSV6eSmdRkjU3xScLbSUJievjdr9QQo1x-_fL_7PWPKfv6hG1BdX0bfTfsejROQX4ATWrHGKC5c5lguZuRoxtyNyNynJGU9uK0QndJx6FgfwF4CQ4W</recordid><startdate>20230504</startdate><enddate>20230504</enddate><creator>Mitrovský, Ondřej</creator><creator>Myslivcová, Denisa</creator><creator>Macháčková-Lopotová, Tereza</creator><creator>Obr, Adam</creator><creator>Čermáková, Kamila</creator><creator>Ransdorfová, Šárka</creator><creator>Březinová, Jana</creator><creator>Klamová, Hana</creator><creator>Žáčková, Markéta</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-0057-076X</orcidid></search><sort><creationdate>20230504</creationdate><title>Inhibition of casein kinase 2 induces cell death in tyrosine kinase inhibitor resistant chronic myelogenous leukemia cells</title><author>Mitrovský, Ondřej ; Myslivcová, Denisa ; Macháčková-Lopotová, Tereza ; Obr, Adam ; Čermáková, Kamila ; Ransdorfová, Šárka ; Březinová, Jana ; Klamová, Hana ; Žáčková, Markéta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c693t-abca32fab9f1c2f929076d76ccfbe0614418a1634ca91862e0757e9b3ca131173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Abl protein</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>BCR protein</topic><topic>Biochemistry</topic><topic>Biology and Life Sciences</topic><topic>Blood cells</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Casein</topic><topic>Casein Kinase II</topic><topic>Cell Death</topic><topic>Cell growth</topic><topic>Cell viability</topic><topic>Chronic myeloid leukemia</topic><topic>Dasatinib - pharmacology</topic><topic>Drug Resistance, Neoplasm</topic><topic>Enzyme inhibitors</topic><topic>Experiments</topic><topic>Fusion protein</topic><topic>Fusion Proteins, bcr-abl - metabolism</topic><topic>Health aspects</topic><topic>Heat shock proteins</topic><topic>Humans</topic><topic>Imatinib</topic><topic>Imatinib Mesylate - pharmacology</topic><topic>Kinases</topic><topic>Leukemia</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy</topic><topic>Leukocytes</topic><topic>Medicine and Health Sciences</topic><topic>Mutation</topic><topic>Myeloid leukemia</topic><topic>Myeloproliferative diseases</topic><topic>Nilotinib</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Phenols</topic><topic>Phosphorylation</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein-tyrosine kinase</topic><topic>Proteins</topic><topic>Research and Analysis Methods</topic><topic>Tyrosine</topic><topic>Tyrosine Kinase Inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mitrovský, Ondřej</creatorcontrib><creatorcontrib>Myslivcová, Denisa</creatorcontrib><creatorcontrib>Macháčková-Lopotová, Tereza</creatorcontrib><creatorcontrib>Obr, Adam</creatorcontrib><creatorcontrib>Čermáková, Kamila</creatorcontrib><creatorcontrib>Ransdorfová, Šárka</creatorcontrib><creatorcontrib>Březinová, Jana</creatorcontrib><creatorcontrib>Klamová, Hana</creatorcontrib><creatorcontrib>Žáčková, Markéta</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints Resource Center</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Databases</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mitrovský, Ondřej</au><au>Myslivcová, Denisa</au><au>Macháčková-Lopotová, Tereza</au><au>Obr, Adam</au><au>Čermáková, Kamila</au><au>Ransdorfová, Šárka</au><au>Březinová, Jana</au><au>Klamová, Hana</au><au>Žáčková, Markéta</au><au>Kancha, Rama Krishna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of casein kinase 2 induces cell death in tyrosine kinase inhibitor resistant chronic myelogenous leukemia cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2023-05-04</date><risdate>2023</risdate><volume>18</volume><issue>5</issue><spage>e0284876</spage><epage>e0284876</epage><pages>e0284876-e0284876</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the BCR-ABL oncogene. Despite the high performance of treatment with tyrosine kinase inhibitors (TKI), about 30% of patients develop resistance to the therapy. To improve the outcomes, identification of new targets of treatment is needed. Here, we explored the Casein Kinase 2 (CK2) as a potential target for CML therapy. Previously, we detected increased phosphorylation of HSP90β Serine 226 in patients non-responding to TKIs imatinib and dasatinib. This site is known to be phosphorylated by CK2, which was also linked to CML resistance to imatinib. In the present work, we established six novel imatinib- and dasatinib-resistant CML cell lines, all of which had increased CK2 activation. A CK2 inhibitor, CX-4945, induced cell death of CML cells in both parental and resistant cell lines. In some cases, CK2 inhibition also potentiated the effects of TKI on the cell metabolic activity. No effects of CK2 inhibition were observed in normal mononuclear blood cells from healthy donors and BCR-ABL negative HL60 cell line. Our data indicate that CK2 kinase supports CML cell viability even in cells with different mechanisms of resistance to TKI, and thus represents a potential target for treatment.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>37141212</pmid><doi>10.1371/journal.pone.0284876</doi><tpages>e0284876</tpages><orcidid>https://orcid.org/0000-0003-0057-076X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2023-05, Vol.18 (5), p.e0284876-e0284876 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2809480424 |
| source | PLoS (Open access); PubMed Central (Open access); MEDLINE; Full-Text Journals in Chemistry (Open access); Directory of Open Access Journals; EZB Electronic Journals Library |
| subjects | Abl protein Antibodies Apoptosis BCR protein Biochemistry Biology and Life Sciences Blood cells Cancer therapies Care and treatment Casein Casein Kinase II Cell Death Cell growth Cell viability Chronic myeloid leukemia Dasatinib - pharmacology Drug Resistance, Neoplasm Enzyme inhibitors Experiments Fusion protein Fusion Proteins, bcr-abl - metabolism Health aspects Heat shock proteins Humans Imatinib Imatinib Mesylate - pharmacology Kinases Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy Leukocytes Medicine and Health Sciences Mutation Myeloid leukemia Myeloproliferative diseases Nilotinib Patient outcomes Patients Phenols Phosphorylation Protein Kinase Inhibitors - pharmacology Protein-tyrosine kinase Proteins Research and Analysis Methods Tyrosine Tyrosine Kinase Inhibitors |
| title | Inhibition of casein kinase 2 induces cell death in tyrosine kinase inhibitor resistant chronic myelogenous leukemia cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-11-29T14%3A43%3A55IST&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=Inhibition%20of%20casein%20kinase%202%20induces%20cell%20death%20in%20tyrosine%20kinase%20inhibitor%20resistant%20chronic%20myelogenous%20leukemia%20cells&rft.jtitle=PloS%20one&rft.au=Mitrovsk%C3%BD,%20Ond%C5%99ej&rft.date=2023-05-04&rft.volume=18&rft.issue=5&rft.spage=e0284876&rft.epage=e0284876&rft.pages=e0284876-e0284876&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0284876&rft_dat=%3Cgale_plos_%3EA748058752%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=2809480424&rft_id=info:pmid/37141212&rft_galeid=A748058752&rft_doaj_id=oai_doaj_org_article_bd7d2e3660b04a6fbabf4e0148eba6b9&rfr_iscdi=true |