The potential of palbociclib for the treatment of FLT3-ITD+ AML

Iris Uras, PhD of the University of Veterinary Medicine, Vienna, Austria discusses an article published in Blood on using palbociclib for the treatment of FLT3-ITD+ acute myeloid leukemia (AML) cells. Mutations of the Fms related tyrosine kinase 3 (FLT3) gene is a frequent event in AML and usually involves internal tandem duplications (ITD) of the juxtamembrane domain or or point mutations of the tyrosine kinase domain (TKD). Further, according to Dr Uras, up to 30% of AML patients harbor a FLT3-ITD mutation, which is associated with a high propensity to relapse after remission in children and adults with AML. Dr Uras outlines the rationale behind the interest in FLT3 inhibitors and how the clinical impact of FLT3 inhibitors has not been as hoped to date. The study published in Blood, offers a novel therapeutic window to specifically target and kill AML cells with the FLT3-ITD+ mutation according to Dr Uras. The tumor-promoting enzyme CDK6 directly regulates and initiates the production of FLT3, which leads to the disease. Palbociclib is approved by the US Food and Drug Administration (FDA) for the treatment of breast cancer and in this study, was found to block the activity of CDK6 and impair FLT3 expression. Palbociclib also stops the production of the PIM1 kinase. Dr Uras further outlines the next steps, which includes addressing the question of whether the findings can be extended to other FLT3 mutations. Recorded via video conference.
Article available here: http://www.bloodjournal.org/content/early/2016/04/20/blood-2015-11-683581