Skip to main content
Open Access Publications from the University of California


UCLA Previously Published Works bannerUCLA

miR-155 promotes FLT3-ITD-induced myeloproliferative disease through inhibition of the interferon response.

  • Author(s): Wallace, Jared A
  • Kagele, Dominique A
  • Eiring, Anna M
  • Kim, Carissa N
  • Hu, Ruozhen
  • Runtsch, Marah C
  • Alexander, Margaret
  • Huffaker, Thomas B
  • Lee, Soh-Hyun
  • Patel, Ami B
  • Mosbruger, Timothy L
  • Voth, Warren P
  • Rao, Dinesh S
  • Miles, Rodney R
  • Round, June L
  • Deininger, Michael W
  • O'Connell, Ryan M
  • et al.

Published Web Location
No data is associated with this publication.

FLT3-ITD+ acute myeloid leukemia (AML) accounts for ∼25% of all AML cases and is a subtype that carries a poor prognosis. microRNA-155 (miR-155) is specifically overexpressed in FLT3-ITD+ AML compared with FLT3 wild-type (FLT3-WT) AML and is critical for the growth of FLT3-ITD+ AML cells in vitro. However, miR-155's role in regulating FLT3-ITD-mediated disease in vivo remains unclear. In this study, we used a genetic mouse model to determine whether miR-155 influences the development of FLT3-ITD-induced myeloproliferative disease. Results indicate that miR-155 promotes FLT3-ITD-induced myeloid expansion in the bone marrow, spleen, and peripheral blood. Mechanistically, miR-155 increases proliferation of the hematopoietic stem and progenitor cell compartments by reducing the growth-inhibitory effects of the interferon (IFN) response, and this involves targeting of Cebpb. Consistent with our observations in mice, primary FLT3-ITD+ AML clinical samples have significantly higher miR-155 levels and a lower IFN response compared with FLT3-WT AML samples. Further, inhibition of miR-155 in FLT3-ITD+ AML cell lines using CRISPR/Cas9, or primary FLT3-ITD+ AML samples using locked nucleic acid antisense inhibitors, results in an elevated IFN response and reduces colony formation. Altogether, our data reveal that miR-155 collaborates with FLT3-ITD to promote myeloid cell expansion in vivo and that this involves a multitarget mechanism that includes repression of IFN signaling.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Item not freely available? Link broken?
Report a problem accessing this item