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

On Monday 3^rd April, at the 107^th 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.