General AML|FLT3

AACR 2017: Poster 2380/22 – Insertion mutations in the tyrosine kinase domain of FLT3 in AML

On Monday 3rd April, at the 107th American Association for Cancer Research (AACR) annual meeting in Washington, DC, USA, there was a poster session focused on “Cell Growth Signaling Pathways”. During this session, a poster (2380/22) titled “Insertion mutations in the tyrosine kinase domain of FLT3 display a higher oncogenic potential than the D835Y mutation in acute myeloid leukemia” by Alissa Marhäll from Lund University, Sweden, and colleagues was on display.

FMS-Like Tyrosine Kinase 3 (FLT3) mutation is expressed in approximately 30% of Acute Myeloid Leukemia (AML) patients. Major mutations in FLT3 include point mutations (D835Y-TKD) and Internal Tandem Duplication Mutation (ITD) with the latter subdivided further by location either at the juxtamembrane domain (ITD-JM) or at the Tyrosine Kinase Domain (ITD-TKD). Marhäll A. et al., aimed to understand whether ITD-TKD mutations play a role in leukemogenesis.

 The key results were:
  • Compared to D835Y-TKD, increased cell proliferation and survival was observed in Ba/F3 cells (expressed mutant ITD constructs in JMD and TKD)
  • STAT5 and AKT phosphorylation were selectively enhanced by ITD-TKD
  • Compared to ITD-TKD, Ba/F3 cells expressing D835Y mutant had an impaired capacity to form colonies

The authors concluded by stating that “ITD-TKD mutations have a stronger transforming potential than other TKD mutations” in AML.

References
  1. Marhäll A. et al. Insertion mutations in the tyrosine kinase domain of FLT3 display a higher oncogenic potential than the D835Y mutation in acute myeloid leukemia [ Poster]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; 2017. Poster nr [2380/22].