Bone marrow stromal cells modulate mouse ENT1 activity and protect leukemia cells from cytarabine induced apoptosis
Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and dru...
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| Veröffentlicht in: | PloS one 2012-05, Vol.7 (5), p.e37203 |
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| creator | Macanas-Pirard, Patricia Leisewitz, Andrea Broekhuizen, Richard Cautivo, Kelly Barriga, Francisco M Leisewitz, Francisco Gidi, Victoria Riquelme, Erick Montecinos, Viviana P Swett, Pilar Besa, Pelayo Ramirez, Pablo Ocqueteau, Mauricio Kalergis, Alexis M Holt, Matthew Rettig, Michael DiPersio, John F Nervi, Bruno |
| description | Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and drug resistance. In this study, we propose to identify mechanisms involved in the chemoprotection conferred by the BM stroma to leukemia cells.
Using a leukemia mouse model and a human leukemia cell line, we studied the interaction of leukemia cells with the BM microenvironment. We evaluated in vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry and western blotting. The activity of the equilibrative nucleoside transporter 1 (ENT1), responsible for cytarabine cell incorporation, was investigated by measuring transport and intracellular accumulation of (3)H-adenosine.
Leukemia cell mobilization from the bone marrow into peripheral blood in vivo using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to cytarabine, which translated into a prolonged survival advantage in our mouse leukemia model. In vitro, the BM stromal cells secreted a soluble factor that mediated significant chemoprotection to leukemia cells from cytarabine induced apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine. No protection was observed when radiation or other cytotoxic agents such as etoposide, cisplatin and 5-fluorouracil were used.
The BM stroma secretes a soluble factor that significantly protects leukemia cells from cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the chemo-protective effects mediated by the BM microenvironment may enhance the benefit of conventional chemotherapy for patients with AML. |
| doi_str_mv | 10.1371/journal.pone.0037203 |
| format | Article |
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Using a leukemia mouse model and a human leukemia cell line, we studied the interaction of leukemia cells with the BM microenvironment. We evaluated in vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry and western blotting. The activity of the equilibrative nucleoside transporter 1 (ENT1), responsible for cytarabine cell incorporation, was investigated by measuring transport and intracellular accumulation of (3)H-adenosine.
Leukemia cell mobilization from the bone marrow into peripheral blood in vivo using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to cytarabine, which translated into a prolonged survival advantage in our mouse leukemia model. In vitro, the BM stromal cells secreted a soluble factor that mediated significant chemoprotection to leukemia cells from cytarabine induced apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine. No protection was observed when radiation or other cytotoxic agents such as etoposide, cisplatin and 5-fluorouracil were used.
The BM stroma secretes a soluble factor that significantly protects leukemia cells from cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the chemo-protective effects mediated by the BM microenvironment may enhance the benefit of conventional chemotherapy for patients with AML.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0037203</identifier><identifier>PMID: 22629369</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>5-Fluorouracil ; Acute myeloid leukemia ; Adenosine ; Analysis ; Animals ; Antimetabolites, Antineoplastic - pharmacology ; Antimetabolites, Antineoplastic - therapeutic use ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Biology ; Bone marrow ; Bone Marrow Cells - drug effects ; Bone Marrow Cells - metabolism ; Cancer ; Cancer prevention ; Cancer research ; Cancer therapies ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell survival ; Cell Survival - drug effects ; Chemoprotection ; Chemotherapy ; Cisplatin ; CXCR4 protein ; Cytarabine ; Cytarabine - pharmacology ; Cytarabine - therapeutic use ; Cytometry ; Cytotoxic agents ; Cytotoxicity ; Drug resistance ; Equilibrative Nucleoside Transporter 1 - metabolism ; Etoposide ; Flavonoids ; Flow cytometry ; Humans ; Immunology ; Immunotherapy ; Leukemia ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - metabolism ; Leukemia, Myeloid, Acute - pathology ; Medicine ; Mice ; Myeloid leukemia ; Nucleoside transporter ; Nucleosides ; Oncology ; Patients ; Peripheral blood ; Proteins ; Radiation ; Stromal cells ; Stromal Cells - drug effects ; Stromal Cells - metabolism ; Survival ; Transporter ; Tumor Cells, Cultured ; Western blotting</subject><ispartof>PloS one, 2012-05, Vol.7 (5), p.e37203</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Macanas-Pirard et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Macanas-Pirard et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-60bbaad3cf98569031abe001fd25ee2ac39839e362924e2ea577592e1eae544c3</citedby><cites>FETCH-LOGICAL-c692t-60bbaad3cf98569031abe001fd25ee2ac39839e362924e2ea577592e1eae544c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358339/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358339/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22629369$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bunting, Kevin D.</contributor><creatorcontrib>Macanas-Pirard, Patricia</creatorcontrib><creatorcontrib>Leisewitz, Andrea</creatorcontrib><creatorcontrib>Broekhuizen, Richard</creatorcontrib><creatorcontrib>Cautivo, Kelly</creatorcontrib><creatorcontrib>Barriga, Francisco M</creatorcontrib><creatorcontrib>Leisewitz, Francisco</creatorcontrib><creatorcontrib>Gidi, Victoria</creatorcontrib><creatorcontrib>Riquelme, Erick</creatorcontrib><creatorcontrib>Montecinos, Viviana P</creatorcontrib><creatorcontrib>Swett, Pilar</creatorcontrib><creatorcontrib>Besa, Pelayo</creatorcontrib><creatorcontrib>Ramirez, Pablo</creatorcontrib><creatorcontrib>Ocqueteau, Mauricio</creatorcontrib><creatorcontrib>Kalergis, Alexis M</creatorcontrib><creatorcontrib>Holt, Matthew</creatorcontrib><creatorcontrib>Rettig, Michael</creatorcontrib><creatorcontrib>DiPersio, John F</creatorcontrib><creatorcontrib>Nervi, Bruno</creatorcontrib><title>Bone marrow stromal cells modulate mouse ENT1 activity and protect leukemia cells from cytarabine induced apoptosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and drug resistance. In this study, we propose to identify mechanisms involved in the chemoprotection conferred by the BM stroma to leukemia cells.
Using a leukemia mouse model and a human leukemia cell line, we studied the interaction of leukemia cells with the BM microenvironment. We evaluated in vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry and western blotting. The activity of the equilibrative nucleoside transporter 1 (ENT1), responsible for cytarabine cell incorporation, was investigated by measuring transport and intracellular accumulation of (3)H-adenosine.
Leukemia cell mobilization from the bone marrow into peripheral blood in vivo using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to cytarabine, which translated into a prolonged survival advantage in our mouse leukemia model. In vitro, the BM stromal cells secreted a soluble factor that mediated significant chemoprotection to leukemia cells from cytarabine induced apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine. No protection was observed when radiation or other cytotoxic agents such as etoposide, cisplatin and 5-fluorouracil were used.
The BM stroma secretes a soluble factor that significantly protects leukemia cells from cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the chemo-protective effects mediated by the BM microenvironment may enhance the benefit of conventional chemotherapy for patients with AML.</description><subject>5-Fluorouracil</subject><subject>Acute myeloid leukemia</subject><subject>Adenosine</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antimetabolites, Antineoplastic - pharmacology</subject><subject>Antimetabolites, Antineoplastic - therapeutic use</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Biology</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - drug effects</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Cancer</subject><subject>Cancer prevention</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell survival</subject><subject>Cell Survival - drug effects</subject><subject>Chemoprotection</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>CXCR4 protein</subject><subject>Cytarabine</subject><subject>Cytarabine - pharmacology</subject><subject>Cytarabine - therapeutic use</subject><subject>Cytometry</subject><subject>Cytotoxic agents</subject><subject>Cytotoxicity</subject><subject>Drug resistance</subject><subject>Equilibrative Nucleoside Transporter 1 - metabolism</subject><subject>Etoposide</subject><subject>Flavonoids</subject><subject>Flow cytometry</subject><subject>Humans</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - drug therapy</subject><subject>Leukemia, Myeloid, Acute - metabolism</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Medicine</subject><subject>Mice</subject><subject>Myeloid leukemia</subject><subject>Nucleoside transporter</subject><subject>Nucleosides</subject><subject>Oncology</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Proteins</subject><subject>Radiation</subject><subject>Stromal cells</subject><subject>Stromal Cells - 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pharmacology</topic><topic>Antimetabolites, Antineoplastic - therapeutic use</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>Biology</topic><topic>Bone marrow</topic><topic>Bone Marrow Cells - drug effects</topic><topic>Bone Marrow Cells - metabolism</topic><topic>Cancer</topic><topic>Cancer prevention</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell survival</topic><topic>Cell Survival - drug effects</topic><topic>Chemoprotection</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>CXCR4 protein</topic><topic>Cytarabine</topic><topic>Cytarabine - pharmacology</topic><topic>Cytarabine - therapeutic use</topic><topic>Cytometry</topic><topic>Cytotoxic agents</topic><topic>Cytotoxicity</topic><topic>Drug resistance</topic><topic>Equilibrative Nucleoside Transporter 1 - metabolism</topic><topic>Etoposide</topic><topic>Flavonoids</topic><topic>Flow cytometry</topic><topic>Humans</topic><topic>Immunology</topic><topic>Immunotherapy</topic><topic>Leukemia</topic><topic>Leukemia, Myeloid, Acute - drug therapy</topic><topic>Leukemia, Myeloid, Acute - metabolism</topic><topic>Leukemia, Myeloid, Acute - pathology</topic><topic>Medicine</topic><topic>Mice</topic><topic>Myeloid leukemia</topic><topic>Nucleoside transporter</topic><topic>Nucleosides</topic><topic>Oncology</topic><topic>Patients</topic><topic>Peripheral blood</topic><topic>Proteins</topic><topic>Radiation</topic><topic>Stromal cells</topic><topic>Stromal Cells - drug effects</topic><topic>Stromal Cells - metabolism</topic><topic>Survival</topic><topic>Transporter</topic><topic>Tumor Cells, Cultured</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Macanas-Pirard, Patricia</creatorcontrib><creatorcontrib>Leisewitz, Andrea</creatorcontrib><creatorcontrib>Broekhuizen, Richard</creatorcontrib><creatorcontrib>Cautivo, Kelly</creatorcontrib><creatorcontrib>Barriga, Francisco M</creatorcontrib><creatorcontrib>Leisewitz, Francisco</creatorcontrib><creatorcontrib>Gidi, Victoria</creatorcontrib><creatorcontrib>Riquelme, Erick</creatorcontrib><creatorcontrib>Montecinos, Viviana P</creatorcontrib><creatorcontrib>Swett, Pilar</creatorcontrib><creatorcontrib>Besa, Pelayo</creatorcontrib><creatorcontrib>Ramirez, Pablo</creatorcontrib><creatorcontrib>Ocqueteau, Mauricio</creatorcontrib><creatorcontrib>Kalergis, Alexis M</creatorcontrib><creatorcontrib>Holt, Matthew</creatorcontrib><creatorcontrib>Rettig, Michael</creatorcontrib><creatorcontrib>DiPersio, John F</creatorcontrib><creatorcontrib>Nervi, Bruno</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</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>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 Edition)</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 Central</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 Korea</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</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>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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</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>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Macanas-Pirard, Patricia</au><au>Leisewitz, Andrea</au><au>Broekhuizen, Richard</au><au>Cautivo, Kelly</au><au>Barriga, Francisco M</au><au>Leisewitz, Francisco</au><au>Gidi, Victoria</au><au>Riquelme, Erick</au><au>Montecinos, Viviana P</au><au>Swett, Pilar</au><au>Besa, Pelayo</au><au>Ramirez, Pablo</au><au>Ocqueteau, Mauricio</au><au>Kalergis, Alexis M</au><au>Holt, Matthew</au><au>Rettig, Michael</au><au>DiPersio, John F</au><au>Nervi, Bruno</au><au>Bunting, Kevin D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone marrow stromal cells modulate mouse ENT1 activity and protect leukemia cells from cytarabine induced apoptosis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-05-22</date><risdate>2012</risdate><volume>7</volume><issue>5</issue><spage>e37203</spage><pages>e37203-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and drug resistance. In this study, we propose to identify mechanisms involved in the chemoprotection conferred by the BM stroma to leukemia cells.
Using a leukemia mouse model and a human leukemia cell line, we studied the interaction of leukemia cells with the BM microenvironment. We evaluated in vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry and western blotting. The activity of the equilibrative nucleoside transporter 1 (ENT1), responsible for cytarabine cell incorporation, was investigated by measuring transport and intracellular accumulation of (3)H-adenosine.
Leukemia cell mobilization from the bone marrow into peripheral blood in vivo using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to cytarabine, which translated into a prolonged survival advantage in our mouse leukemia model. In vitro, the BM stromal cells secreted a soluble factor that mediated significant chemoprotection to leukemia cells from cytarabine induced apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine. No protection was observed when radiation or other cytotoxic agents such as etoposide, cisplatin and 5-fluorouracil were used.
The BM stroma secretes a soluble factor that significantly protects leukemia cells from cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the chemo-protective effects mediated by the BM microenvironment may enhance the benefit of conventional chemotherapy for patients with AML.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22629369</pmid><doi>10.1371/journal.pone.0037203</doi><tpages>e37203</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-05, Vol.7 (5), p.e37203 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1325012838 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 5-Fluorouracil Acute myeloid leukemia Adenosine Analysis Animals Antimetabolites, Antineoplastic - pharmacology Antimetabolites, Antineoplastic - therapeutic use Apoptosis Apoptosis - drug effects Apoptosis - physiology Biology Bone marrow Bone Marrow Cells - drug effects Bone Marrow Cells - metabolism Cancer Cancer prevention Cancer research Cancer therapies Cell Line, Tumor Cell Proliferation - drug effects Cell survival Cell Survival - drug effects Chemoprotection Chemotherapy Cisplatin CXCR4 protein Cytarabine Cytarabine - pharmacology Cytarabine - therapeutic use Cytometry Cytotoxic agents Cytotoxicity Drug resistance Equilibrative Nucleoside Transporter 1 - metabolism Etoposide Flavonoids Flow cytometry Humans Immunology Immunotherapy Leukemia Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - metabolism Leukemia, Myeloid, Acute - pathology Medicine Mice Myeloid leukemia Nucleoside transporter Nucleosides Oncology Patients Peripheral blood Proteins Radiation Stromal cells Stromal Cells - drug effects Stromal Cells - metabolism Survival Transporter Tumor Cells, Cultured Western blotting |
| title | Bone marrow stromal cells modulate mouse ENT1 activity and protect leukemia cells from cytarabine induced apoptosis |
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