Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages

Autores
Borge, Mercedes; Almejún, María Belén; Podaza, Enrique Arturo; Colado, Ana; Fernández Grecco, Horacio; Cabrejo, María; Bezares, Raimundo F.; Giordano, Mirta Nilda; Gamberale, Romina
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have read with great interest the recent article of Kohrt, H.E. et al1 showing that Ibrutinib prevented NK cell mediated cytotoxicity of antibody-coated CLL cells in vitro. They also found that the concurrent treatment with Ibrutinib and rituximab or trastuzumab reduces the therapeutic efficacy of both anti-CD20 antibodies in a mouse model, while the sequential treatment with Ibrutinib and rituximab restored its anti-lymphoma activity. Since macrophages are the most important effector cells in CD20-directed cytotoxicity in murine models2,3 and they probably play a key role in human anti-CD20 therapy4,5, we determined whether Ibrutinib interferes the capacity of human macrophages to mediate phagocytosis of rituximab-coated CLL cells. To address this issue, macrophages differentiated from healthy peripheral blood monocytes were treated with or without Ibrutinib for 30 minutes and then cultured for 1, 2 or 3 hours with CFSE-labeled CLL cells or rituximab-coated CFSE-labeled CLL cells. Then, cells were tripsinized and the proportion of macrophages that have taken up CFSE-labeled CLL cells (CFSE+ macrophages) were scored by flow cytometry and verified using confocal microscopy, as previously described6. As expected, we found that the cultures with rituximab-coated CLL cells showed the highest percentage of CFSE+ macrophages, which increase in a time dependent manner (open circles in Figure 1A). Ibrutinib was able to reduce these values in all the times evaluated (solid circles in Figure 1A). Low percentages of CFSE+ macrophages were obtained in cultures with uncoated CLL cells, which were not modified by Ibrutinib (open and solid squares in Figure 1A). In addition, we found that Ibrutinib diminishes the percentage of CFSE+ macrophages in the cultures with rituximab-coated cells in a dose dependent manner (Figure 1B), which was not associated to a decreased viability of the macrophages (not shown). Moreover, the inhibitory effect of Ibrutinib was not limited to rituximab since comparable results were obtained when campath-coated CFSE-labeled CLL cells were employed (Figure 1C). Similar results were found when macrophages from CLL patients were used: mean±SE of the % of CFSE+ macrophages: 26.8 ± 2.1 vs, 17.3 ± 2.7 vs 10.8 ± 0.7 for rituximab-coated CFSE-labeled CLL cells alone, with 0.5μM or 5μM of Ibrutinib (n= 6). Representative dot plots are shown in Figure 1D. The results obtained by flow cytometry analysis were validated by confocal microscopy quantifying the number of macrophages that engulfed at least one tumor target cell (Figure 1E). A representative experiment is shown in Figure 1F. In addition, by performing a binding assay at 4oC, we confirmed that Ibrutinib did not reduce the binding of rituximab-coated CFSE-labeled CLL cells to macrophages (Figure 1G). Interestingly, while the presence of Ibrutinib during the assay impairs the phagocytosis of rituximab-coated CLL cells, when Ibrutinib was washed out, macrophages recovered their phagocytic capacity in a time-dependent manner (Figure 1H). In conclusion we found that the presence of Ibrutinib impairs the phagocytosis of rituximab-opsonized CLL cells by human macrophages, which was restored when the inhibitor was removed from the cultures. Our results, and those obtained by Kohrt et al1 suggest that the sequential administration of Ibrutinib followed by rituximab, and not the concurrent treatment of the patients with these agents, might enhance their anti-tumor activity in vivo.
Fil: Borge, Mercedes. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Almejún, María Belén. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Cátedra de Microbiología, Parasitología e Inmunología; Argentina
Fil: Podaza, Enrique Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Colado, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Fernández Grecco, Horacio. Sanatorio Municipal Dr. Julio Méndez; Argentina
Fil: Cabrejo, María. Sanatorio Municipal Dr. Julio Méndez; Argentina
Fil: Bezares, Raimundo F.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; Argentina
Fil: Giordano, Mirta Nilda. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Materia
IBRUTINIB
PHAGOCYTOSIS
RITUXIMAB-DEPENDENT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/39828

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network_name_str CONICET Digital (CONICET)
spelling Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophagesBorge, MercedesAlmejún, María BelénPodaza, Enrique ArturoColado, AnaFernández Grecco, HoracioCabrejo, MaríaBezares, Raimundo F.Giordano, Mirta NildaGamberale, RominaIBRUTINIBPHAGOCYTOSISRITUXIMAB-DEPENDENThttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We have read with great interest the recent article of Kohrt, H.E. et al1 showing that Ibrutinib prevented NK cell mediated cytotoxicity of antibody-coated CLL cells in vitro. They also found that the concurrent treatment with Ibrutinib and rituximab or trastuzumab reduces the therapeutic efficacy of both anti-CD20 antibodies in a mouse model, while the sequential treatment with Ibrutinib and rituximab restored its anti-lymphoma activity. Since macrophages are the most important effector cells in CD20-directed cytotoxicity in murine models2,3 and they probably play a key role in human anti-CD20 therapy4,5, we determined whether Ibrutinib interferes the capacity of human macrophages to mediate phagocytosis of rituximab-coated CLL cells. To address this issue, macrophages differentiated from healthy peripheral blood monocytes were treated with or without Ibrutinib for 30 minutes and then cultured for 1, 2 or 3 hours with CFSE-labeled CLL cells or rituximab-coated CFSE-labeled CLL cells. Then, cells were tripsinized and the proportion of macrophages that have taken up CFSE-labeled CLL cells (CFSE+ macrophages) were scored by flow cytometry and verified using confocal microscopy, as previously described6. As expected, we found that the cultures with rituximab-coated CLL cells showed the highest percentage of CFSE+ macrophages, which increase in a time dependent manner (open circles in Figure 1A). Ibrutinib was able to reduce these values in all the times evaluated (solid circles in Figure 1A). Low percentages of CFSE+ macrophages were obtained in cultures with uncoated CLL cells, which were not modified by Ibrutinib (open and solid squares in Figure 1A). In addition, we found that Ibrutinib diminishes the percentage of CFSE+ macrophages in the cultures with rituximab-coated cells in a dose dependent manner (Figure 1B), which was not associated to a decreased viability of the macrophages (not shown). Moreover, the inhibitory effect of Ibrutinib was not limited to rituximab since comparable results were obtained when campath-coated CFSE-labeled CLL cells were employed (Figure 1C). Similar results were found when macrophages from CLL patients were used: mean±SE of the % of CFSE+ macrophages: 26.8 ± 2.1 vs, 17.3 ± 2.7 vs 10.8 ± 0.7 for rituximab-coated CFSE-labeled CLL cells alone, with 0.5μM or 5μM of Ibrutinib (n= 6). Representative dot plots are shown in Figure 1D. The results obtained by flow cytometry analysis were validated by confocal microscopy quantifying the number of macrophages that engulfed at least one tumor target cell (Figure 1E). A representative experiment is shown in Figure 1F. In addition, by performing a binding assay at 4oC, we confirmed that Ibrutinib did not reduce the binding of rituximab-coated CFSE-labeled CLL cells to macrophages (Figure 1G). Interestingly, while the presence of Ibrutinib during the assay impairs the phagocytosis of rituximab-coated CLL cells, when Ibrutinib was washed out, macrophages recovered their phagocytic capacity in a time-dependent manner (Figure 1H). In conclusion we found that the presence of Ibrutinib impairs the phagocytosis of rituximab-opsonized CLL cells by human macrophages, which was restored when the inhibitor was removed from the cultures. Our results, and those obtained by Kohrt et al1 suggest that the sequential administration of Ibrutinib followed by rituximab, and not the concurrent treatment of the patients with these agents, might enhance their anti-tumor activity in vivo.Fil: Borge, Mercedes. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Almejún, María Belén. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Cátedra de Microbiología, Parasitología e Inmunología; ArgentinaFil: Podaza, Enrique Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Colado, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fernández Grecco, Horacio. Sanatorio Municipal Dr. Julio Méndez; ArgentinaFil: Cabrejo, María. Sanatorio Municipal Dr. Julio Méndez; ArgentinaFil: Bezares, Raimundo F.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Giordano, Mirta Nilda. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFerrata Storti Foundation2015-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39828Borge, Mercedes; Almejún, María Belén; Podaza, Enrique Arturo; Colado, Ana; Fernández Grecco, Horacio; et al.; Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages; Ferrata Storti Foundation; Haematologica; 100; 4; 1-2015; 1-30390-60781592-8721CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.haematologica.org/content/100/4/e140.longinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380736/info:eu-repo/semantics/altIdentifier/doi/10.3324/haematol.2014.119669info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:57:42Zoai:ri.conicet.gov.ar:11336/39828instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:57:42.936CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages
title Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages
spellingShingle Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages
Borge, Mercedes
IBRUTINIB
PHAGOCYTOSIS
RITUXIMAB-DEPENDENT
title_short Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages
title_full Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages
title_fullStr Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages
title_full_unstemmed Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages
title_sort Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages
dc.creator.none.fl_str_mv Borge, Mercedes
Almejún, María Belén
Podaza, Enrique Arturo
Colado, Ana
Fernández Grecco, Horacio
Cabrejo, María
Bezares, Raimundo F.
Giordano, Mirta Nilda
Gamberale, Romina
author Borge, Mercedes
author_facet Borge, Mercedes
Almejún, María Belén
Podaza, Enrique Arturo
Colado, Ana
Fernández Grecco, Horacio
Cabrejo, María
Bezares, Raimundo F.
Giordano, Mirta Nilda
Gamberale, Romina
author_role author
author2 Almejún, María Belén
Podaza, Enrique Arturo
Colado, Ana
Fernández Grecco, Horacio
Cabrejo, María
Bezares, Raimundo F.
Giordano, Mirta Nilda
Gamberale, Romina
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv IBRUTINIB
PHAGOCYTOSIS
RITUXIMAB-DEPENDENT
topic IBRUTINIB
PHAGOCYTOSIS
RITUXIMAB-DEPENDENT
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We have read with great interest the recent article of Kohrt, H.E. et al1 showing that Ibrutinib prevented NK cell mediated cytotoxicity of antibody-coated CLL cells in vitro. They also found that the concurrent treatment with Ibrutinib and rituximab or trastuzumab reduces the therapeutic efficacy of both anti-CD20 antibodies in a mouse model, while the sequential treatment with Ibrutinib and rituximab restored its anti-lymphoma activity. Since macrophages are the most important effector cells in CD20-directed cytotoxicity in murine models2,3 and they probably play a key role in human anti-CD20 therapy4,5, we determined whether Ibrutinib interferes the capacity of human macrophages to mediate phagocytosis of rituximab-coated CLL cells. To address this issue, macrophages differentiated from healthy peripheral blood monocytes were treated with or without Ibrutinib for 30 minutes and then cultured for 1, 2 or 3 hours with CFSE-labeled CLL cells or rituximab-coated CFSE-labeled CLL cells. Then, cells were tripsinized and the proportion of macrophages that have taken up CFSE-labeled CLL cells (CFSE+ macrophages) were scored by flow cytometry and verified using confocal microscopy, as previously described6. As expected, we found that the cultures with rituximab-coated CLL cells showed the highest percentage of CFSE+ macrophages, which increase in a time dependent manner (open circles in Figure 1A). Ibrutinib was able to reduce these values in all the times evaluated (solid circles in Figure 1A). Low percentages of CFSE+ macrophages were obtained in cultures with uncoated CLL cells, which were not modified by Ibrutinib (open and solid squares in Figure 1A). In addition, we found that Ibrutinib diminishes the percentage of CFSE+ macrophages in the cultures with rituximab-coated cells in a dose dependent manner (Figure 1B), which was not associated to a decreased viability of the macrophages (not shown). Moreover, the inhibitory effect of Ibrutinib was not limited to rituximab since comparable results were obtained when campath-coated CFSE-labeled CLL cells were employed (Figure 1C). Similar results were found when macrophages from CLL patients were used: mean±SE of the % of CFSE+ macrophages: 26.8 ± 2.1 vs, 17.3 ± 2.7 vs 10.8 ± 0.7 for rituximab-coated CFSE-labeled CLL cells alone, with 0.5μM or 5μM of Ibrutinib (n= 6). Representative dot plots are shown in Figure 1D. The results obtained by flow cytometry analysis were validated by confocal microscopy quantifying the number of macrophages that engulfed at least one tumor target cell (Figure 1E). A representative experiment is shown in Figure 1F. In addition, by performing a binding assay at 4oC, we confirmed that Ibrutinib did not reduce the binding of rituximab-coated CFSE-labeled CLL cells to macrophages (Figure 1G). Interestingly, while the presence of Ibrutinib during the assay impairs the phagocytosis of rituximab-coated CLL cells, when Ibrutinib was washed out, macrophages recovered their phagocytic capacity in a time-dependent manner (Figure 1H). In conclusion we found that the presence of Ibrutinib impairs the phagocytosis of rituximab-opsonized CLL cells by human macrophages, which was restored when the inhibitor was removed from the cultures. Our results, and those obtained by Kohrt et al1 suggest that the sequential administration of Ibrutinib followed by rituximab, and not the concurrent treatment of the patients with these agents, might enhance their anti-tumor activity in vivo.
Fil: Borge, Mercedes. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Almejún, María Belén. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Cátedra de Microbiología, Parasitología e Inmunología; Argentina
Fil: Podaza, Enrique Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Colado, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Fernández Grecco, Horacio. Sanatorio Municipal Dr. Julio Méndez; Argentina
Fil: Cabrejo, María. Sanatorio Municipal Dr. Julio Méndez; Argentina
Fil: Bezares, Raimundo F.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; Argentina
Fil: Giordano, Mirta Nilda. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
description We have read with great interest the recent article of Kohrt, H.E. et al1 showing that Ibrutinib prevented NK cell mediated cytotoxicity of antibody-coated CLL cells in vitro. They also found that the concurrent treatment with Ibrutinib and rituximab or trastuzumab reduces the therapeutic efficacy of both anti-CD20 antibodies in a mouse model, while the sequential treatment with Ibrutinib and rituximab restored its anti-lymphoma activity. Since macrophages are the most important effector cells in CD20-directed cytotoxicity in murine models2,3 and they probably play a key role in human anti-CD20 therapy4,5, we determined whether Ibrutinib interferes the capacity of human macrophages to mediate phagocytosis of rituximab-coated CLL cells. To address this issue, macrophages differentiated from healthy peripheral blood monocytes were treated with or without Ibrutinib for 30 minutes and then cultured for 1, 2 or 3 hours with CFSE-labeled CLL cells or rituximab-coated CFSE-labeled CLL cells. Then, cells were tripsinized and the proportion of macrophages that have taken up CFSE-labeled CLL cells (CFSE+ macrophages) were scored by flow cytometry and verified using confocal microscopy, as previously described6. As expected, we found that the cultures with rituximab-coated CLL cells showed the highest percentage of CFSE+ macrophages, which increase in a time dependent manner (open circles in Figure 1A). Ibrutinib was able to reduce these values in all the times evaluated (solid circles in Figure 1A). Low percentages of CFSE+ macrophages were obtained in cultures with uncoated CLL cells, which were not modified by Ibrutinib (open and solid squares in Figure 1A). In addition, we found that Ibrutinib diminishes the percentage of CFSE+ macrophages in the cultures with rituximab-coated cells in a dose dependent manner (Figure 1B), which was not associated to a decreased viability of the macrophages (not shown). Moreover, the inhibitory effect of Ibrutinib was not limited to rituximab since comparable results were obtained when campath-coated CFSE-labeled CLL cells were employed (Figure 1C). Similar results were found when macrophages from CLL patients were used: mean±SE of the % of CFSE+ macrophages: 26.8 ± 2.1 vs, 17.3 ± 2.7 vs 10.8 ± 0.7 for rituximab-coated CFSE-labeled CLL cells alone, with 0.5μM or 5μM of Ibrutinib (n= 6). Representative dot plots are shown in Figure 1D. The results obtained by flow cytometry analysis were validated by confocal microscopy quantifying the number of macrophages that engulfed at least one tumor target cell (Figure 1E). A representative experiment is shown in Figure 1F. In addition, by performing a binding assay at 4oC, we confirmed that Ibrutinib did not reduce the binding of rituximab-coated CFSE-labeled CLL cells to macrophages (Figure 1G). Interestingly, while the presence of Ibrutinib during the assay impairs the phagocytosis of rituximab-coated CLL cells, when Ibrutinib was washed out, macrophages recovered their phagocytic capacity in a time-dependent manner (Figure 1H). In conclusion we found that the presence of Ibrutinib impairs the phagocytosis of rituximab-opsonized CLL cells by human macrophages, which was restored when the inhibitor was removed from the cultures. Our results, and those obtained by Kohrt et al1 suggest that the sequential administration of Ibrutinib followed by rituximab, and not the concurrent treatment of the patients with these agents, might enhance their anti-tumor activity in vivo.
publishDate 2015
dc.date.none.fl_str_mv 2015-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/39828
Borge, Mercedes; Almejún, María Belén; Podaza, Enrique Arturo; Colado, Ana; Fernández Grecco, Horacio; et al.; Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages; Ferrata Storti Foundation; Haematologica; 100; 4; 1-2015; 1-3
0390-6078
1592-8721
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39828
identifier_str_mv Borge, Mercedes; Almejún, María Belén; Podaza, Enrique Arturo; Colado, Ana; Fernández Grecco, Horacio; et al.; Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages; Ferrata Storti Foundation; Haematologica; 100; 4; 1-2015; 1-3
0390-6078
1592-8721
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.haematologica.org/content/100/4/e140.long
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380736/
info:eu-repo/semantics/altIdentifier/doi/10.3324/haematol.2014.119669
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Ferrata Storti Foundation
publisher.none.fl_str_mv Ferrata Storti Foundation
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instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
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