Targeting CD38 in acute myeloid leukemia interferes with leukemia trafficking and induces phagocytosis

Abstract Targeting the interaction between leukemic cells and the microenvironment is an appealing approach to enhance the therapeutic efficacy in acute myeloid leukemia (AML). AML infiltration induces a significant release of inflammatory cytokines in the human bone marrow niche which accelerates l...

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Autores principales:	Meike Farber, Yiyang Chen, Lucas Arnold, Michael Möllmann, Eva Boog-Whiteside, Yu-An Lin, H. Christian Reinhardt, Ulrich Dührsen, Maher Hanoun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d97d5af41fbb4c26838feff8bdc564fe
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spelling	oai:doaj.org-article:d97d5af41fbb4c26838feff8bdc564fe2021-11-14T12:22:18ZTargeting CD38 in acute myeloid leukemia interferes with leukemia trafficking and induces phagocytosis10.1038/s41598-021-01300-82045-2322https://doaj.org/article/d97d5af41fbb4c26838feff8bdc564fe2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01300-8https://doaj.org/toc/2045-2322Abstract Targeting the interaction between leukemic cells and the microenvironment is an appealing approach to enhance the therapeutic efficacy in acute myeloid leukemia (AML). AML infiltration induces a significant release of inflammatory cytokines in the human bone marrow niche which accelerates leukemogenesis. As the transmembrane glycoprotein CD38 has been shown to regulate cytokine release, we assessed the anti-leukemic potential of CD38 inhibition in AML. CD38 expression in AML cells proved to depend on microenvironmental cues and could be significantly enforced through addition of tretinoin. In fact, the anti-CD38 antibody daratumumab showed significant cytostatic efficacy in a 3D in vitro triple-culture model of AML, but with modest cell-autonomous cytotoxic activity and independent of CD38 expression level. In line with a predominantly microenvironment-mediated activity of daratumumab in AML, CD38 inhibition significantly induced antibody-dependent phagocytosis and showed interference with AML cell trafficking in vivo in a xenograft transplantation model, but overall lacked robust anti-leukemic effects.Meike FarberYiyang ChenLucas ArnoldMichael MöllmannEva Boog-WhitesideYu-An LinH. Christian ReinhardtUlrich DührsenMaher HanounNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Meike Farber Yiyang Chen Lucas Arnold Michael Möllmann Eva Boog-Whiteside Yu-An Lin H. Christian Reinhardt Ulrich Dührsen Maher Hanoun Targeting CD38 in acute myeloid leukemia interferes with leukemia trafficking and induces phagocytosis
description	Abstract Targeting the interaction between leukemic cells and the microenvironment is an appealing approach to enhance the therapeutic efficacy in acute myeloid leukemia (AML). AML infiltration induces a significant release of inflammatory cytokines in the human bone marrow niche which accelerates leukemogenesis. As the transmembrane glycoprotein CD38 has been shown to regulate cytokine release, we assessed the anti-leukemic potential of CD38 inhibition in AML. CD38 expression in AML cells proved to depend on microenvironmental cues and could be significantly enforced through addition of tretinoin. In fact, the anti-CD38 antibody daratumumab showed significant cytostatic efficacy in a 3D in vitro triple-culture model of AML, but with modest cell-autonomous cytotoxic activity and independent of CD38 expression level. In line with a predominantly microenvironment-mediated activity of daratumumab in AML, CD38 inhibition significantly induced antibody-dependent phagocytosis and showed interference with AML cell trafficking in vivo in a xenograft transplantation model, but overall lacked robust anti-leukemic effects.
format	article
author	Meike Farber Yiyang Chen Lucas Arnold Michael Möllmann Eva Boog-Whiteside Yu-An Lin H. Christian Reinhardt Ulrich Dührsen Maher Hanoun
author_facet	Meike Farber Yiyang Chen Lucas Arnold Michael Möllmann Eva Boog-Whiteside Yu-An Lin H. Christian Reinhardt Ulrich Dührsen Maher Hanoun
author_sort	Meike Farber
title	Targeting CD38 in acute myeloid leukemia interferes with leukemia trafficking and induces phagocytosis
title_short	Targeting CD38 in acute myeloid leukemia interferes with leukemia trafficking and induces phagocytosis
title_full	Targeting CD38 in acute myeloid leukemia interferes with leukemia trafficking and induces phagocytosis
title_fullStr	Targeting CD38 in acute myeloid leukemia interferes with leukemia trafficking and induces phagocytosis
title_full_unstemmed	Targeting CD38 in acute myeloid leukemia interferes with leukemia trafficking and induces phagocytosis
title_sort	targeting cd38 in acute myeloid leukemia interferes with leukemia trafficking and induces phagocytosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d97d5af41fbb4c26838feff8bdc564fe
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Targeting CD38 in acute myeloid leukemia interferes with leukemia trafficking and induces phagocytosis

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