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Hönes, Judith M.; Thivakaran, Aniththa; Botezatu, Lacramioara; Patnana, Pradeep; Castro, Symone Vitoriano da Conceição; Al-Matary, Yahya S.; Schütte, Judith; Fischer, Karen B. I.; Vassen, Lothar; Görgens, André; Dührsen, Ulrich; Giebel, Bernd; Khandanpour, Cyrus

Enforced GFI1 expression impedes human and murine leukemic cell growth

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  • Media type: E-Article
  • Title: Enforced GFI1 expression impedes human and murine leukemic cell growth
  • Contributor: Hönes, Judith M.; Thivakaran, Aniththa; Botezatu, Lacramioara; Patnana, Pradeep; Castro, Symone Vitoriano da Conceição; Al-Matary, Yahya S.; Schütte, Judith; Fischer, Karen B. I.; Vassen, Lothar; Görgens, André; Dührsen, Ulrich; Giebel, Bernd; Khandanpour, Cyrus
  • Published: Springer Science and Business Media LLC, 2017
  • Published in: Scientific Reports, 7 (2017) 1
  • Language: English
  • DOI: 10.1038/s41598-017-15866-9
  • ISSN: 2045-2322
  • Origination:
  • Footnote:
  • Description: AbstractThe differentiation of haematopoietic cells is regulated by a plethora of so-called transcription factors (TFs). Mutations in genes encoding TFs or graded reduction in their expression levels can induce the development of various malignant diseases such as acute myeloid leukaemia (AML). Growth Factor Independence 1 (GFI1) is a transcriptional repressor with key roles in haematopoiesis, including regulating self-renewal of haematopoietic stem cells (HSCs) as well as myeloid and lymphoid differentiation. Analysis of AML patients and different AML mouse models with reducedGFI1gene expression levels revealed a direct link between low GFI1 protein level and accelerated AML development and inferior prognosis. Here, we report that upregulated expression ofGFI1in several widely used leukemic cell lines inhibits their growth and decreases the ability to generate coloniesin vitro. Similarly, elevated expression ofGFI1impedes thein vitroexpansion of murine pre-leukemic cells. Using a humanized AML model, we demonstrate that upregulation ofGFI1expression leads to myeloid differentiation morphologically and immunophenotypically, increased level of apoptosis and reduction in number of cKit+cells. These results suggest that increasing GFI1 level in leukemic cells with lowGFI1expression level could be a therapeutic approach.
  • Access State: Open Access