title: Acute myeloid leukemia cells polarize macrophages towards a leukemia supporting state in a Growth factor independence 1 dependent manner.
abstract: The growth of malignant cells is not only driven by cell-intrinsic factors, but also by the surrounding stroma. Monocytes/Macrophages play an important role in the onset and progression of solid cancers. However, little is known about their role in the development of acute myeloid leukemia, a malignant disease characterized by an aberrant development of the myeloid compartment of the hematopoietic system. It is also unclear which factors are responsible for changing the status of macrophage polarization, thus supporting the growth of malignant cells instead of inhibiting it. We report herein that acute myeloid leukemia leads to the invasion of acute myeloid leukemia-associated macrophages into the bone marrow and spleen of leukemic patients and mice. In different leukemic mouse models, these macrophages support the in vitro expansion of acute myeloid leukemia cell lines better than macrophages from non-leukemic mice. The grade of macrophage infiltration correlates in vivo with the survival of the mice. We found that the transcriptional repressor Growth factor independence 1 is crucial in the process of macrophage polarization, since its absence impedes macrophage polarization towards a leukemia supporting state and favors an anti-tumor state both in vitro and in vivo These results not only suggest that acute myeloid leukemia-associated macrophages play an important role in the progression of acute myeloid leukemia, but also implicate Growth factor independence 1 as a pivotal factor in macrophage polarization. These data may provide new insights and opportunities for novel therapies for acute myeloid leukemia.
authors.affiliation: Department of Hematology, University Hospital of Essen, West German Cancer Center (WTZ).
authors.forename: Yahya S
authors.initials: YS
authors.lastname: Al-Matary
authors.affiliation: Department of Hematology, University Hospital of Essen, West German Cancer Center (WTZ).
authors.forename: Lacramioara
authors.initials: L
authors.lastname: Botezatu
authors.affiliation: Department of Hematology, University Hospital of Essen, West German Cancer Center (WTZ).
authors.forename: Bertram
authors.initials: B
authors.lastname: Opalka
authors.affiliation: Department of Hematology, University Hospital of Essen, West German Cancer Center (WTZ).
authors.forename: Judith M
authors.initials: JM
authors.lastname: Hönes
authors.affiliation: Department of Hematology, University Hospital of Essen, West German Cancer Center (WTZ).
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lams
authors.affiliation: Department of Hematology, University Hospital of Essen, West German Cancer Center (WTZ).
authors.forename: Aniththa
authors.initials: A
authors.lastname: Thivakaran
authors.affiliation: Department of Hematology, University Hospital of Essen, West German Cancer Center (WTZ).
authors.forename: Judith
authors.initials: J
authors.lastname: Schütte
authors.affiliation: Department of Hematology, University Hospital of Essen, West German Cancer Center (WTZ).
authors.forename: Renata
authors.initials: R
authors.lastname: Köster
authors.affiliation: Institute of cell biology (Tumor Research), University Hospital Essen, University of Duisburg-Essen.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lennartz
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University Düsseldorf, University Hospital, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schroeder
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University Düsseldorf, University Hospital, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.affiliation: Department of Hematology, University Hospital of Essen, West German Cancer Center (WTZ).
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.affiliation: Department of Hematology, University Hospital of Essen, West German Cancer Center (WTZ) cyrus.khandanpour@uk-essen.de.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Khandanpour
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000502:physiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000473:pathology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; D014157:Transcription Factors