Sandhöfer Nadine, Bauer Julia, Reiter Katrin, Dufour Annika, Rothenberg Maja, Konstandin Nikola P, Zellmeier Evelyn, Tizazu Belay, Greif Philipp A, Metzeler Klaus H, Hiddemann Wolfgang, Polzer Harald, Spiekermann Karsten
Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.
German Cancer Consortium (DKTK), Heidelberg, Germany.
Sci Rep. 2016 Jun 27;6:28032. doi: 10.1038/srep28032.
In acute myeloid leukemia (AML), the Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes. Recently, a new and recurrent juxtamembrane deletion mutation (p.Q569Vfs2) resulting in a truncated receptor was identified. The mutated receptor is expressed on the cell surface and still binds its ligand but loses the ability to activate ERK signaling. FLT3 p.Q569fs-expressing Ba/F3 cells show no proliferation after ligand stimulation. Furthermore, coexpressed with the FLT3 wild-type (WT) receptor, the truncated receptor suppresses stimulation and activation of the WT receptor. Thus, FLT3 p.Q569Vfs2, to our knowledge, is the first FLT3 mutation with a dominant negative effect on the WT receptor.
在急性髓系白血病（AML）中，Fms样酪氨酸激酶3（FLT3）是最常发生突变的基因之一。最近，一种新的复发性近膜区缺失突变（p.Q569Vfs2）被发现，该突变导致受体截短。突变后的受体在细胞表面表达，仍能结合其配体，但失去了激活ERK信号的能力。表达FLT3 p.Q569fs的Ba/F3细胞在配体刺激后无增殖现象。此外，与FLT3野生型（WT）受体共表达时，截短的受体可抑制WT受体的刺激和激活。因此，据我们所知，FLT3 p.Q569Vfs2是首个对WT受体具有显性负性作用的FLT3突变。
