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Migration arrest of chemoresistant leukemia cells mediated by MRTF-SRF pathway

Authors
  • Morimatsu, Maho1
  • Yamashita, Erika1, 1, 2
  • Seno, Shigeto1
  • Sudo, Takao1, 1, 2
  • Kikuta, Junichi1, 1, 2
  • Mizuno, Hiroki1, 1
  • Okuzaki, Daisuke1, 1
  • Motooka, Daisuke1
  • Ishii, Masaru1, 1, 2
  • 1 Osaka University, Osaka, Japan , Osaka (Japan)
  • 2 National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan , Osaka (Japan)
Type
Published Article
Journal
Inflammation and Regeneration
Publisher
BioMed Central
Publication Date
Jul 06, 2020
Volume
40
Issue
1
Identifiers
DOI: 10.1186/s41232-020-00127-6
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundDormant chemotherapy-resistant leukemia cells can survive for an extended period before relapse. Nevertheless, the mechanisms underlying the development of chemoresistance in vivo remain unclear.MethodsUsing intravital bone imaging, we characterized the behavior of murine acute myeloid leukemia (AML) cells (C1498) in the bone marrow before and after chemotherapy with cytarabine.ResultsProliferative C1498 cells exhibited high motility in the bone marrow. Cytarabine treatment impaired the motility of residual C1498 cells. However, C1498 cells regained their migration potential after relapse. RNA sequencing revealed that cytarabine treatment promoted MRTF-SRF pathway activation. MRTF inhibition using CCG-203971 augmented the anti-tumor effects of chemotherapy in our AML mouse model, as well as suppressed the migration of chemoresistant C1498 cells.ConclusionsThese results provide novel insight into the role of cell migration arrest on the development of chemoresistance in AML, as well as provide a strong rationale for the modulation of cellular motility as a therapeutic target for refractory AML.

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