Details

Autor(en) / Beteiligte

• Wurm, A.A
• Behre, G
• Madan, V
• Tenen, D.G
• Gerloff, D
• Muller-Tidow, C
• Duyster, J
• Niederwieser, D
• Brauer-Hartmann, D
• Hartmann, J.-U
• Katzerke, C
• Grundler, R

Titel

NF-[kappa]B/STAT5/miR-155 network targets PU.1 in FLT3-ITD-driven acute myeloid leukemia.(ORIGINAL ARTICLE)(nuclear factor kappa B/FMS-like tyrosine kinase 3 receptor-internal tandem duplication)

Ist Teil von

• Leukemia, 2015-03, Vol.29 (3), p.535

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Almost 30% of all acute myeloid leukemias (AML) are associated with an internal tandem duplication (ITD) in the juxtamembrane domain of FMS-like tyrosine kinase 3 receptor (FLT3). Patients with FLT3-ITD mutations tend to have a poor prognosis. MicroRNAs (miRNAs) have a pivotal role in myeloid differentiation and leukemia. MiRNA-155 (MiR-155) was found to be upregulated in FLT3-ITD-associated AMLs. In this study, we discovered that FLT3-ITD signaling induces the oncogenic miR-155. We show in vitro and in vivo that miR-155 expression is regulated by FLT3-ITD downstream targets nuclear factor-KB (p65) and signal transducer and activator of transcription 5 (STAT5). Further, we demonstrate that miR-155 targets the myeloid transcription factor PU.1. Knockdown of miR-155 or overexpression of PU.1 blocks proliferation and induces apoptosis of FLT3-ITD-associated leukemic cells. Our data demonstrate a novel network in which FLT3-ITD signaling induces oncogenic miR-155 by p65 and STAT5 in AML, thereby targeting transcription factor PU.1. Leukemia (2015) 29, 535-547; doi: 10.1038/leu.2014.231