Targeting miR-155 in FLT3-ITD mutated AML: ready for prime time?

The most common genetic aberration in AML is a gain-of-function mutation in the FMS-like tyrosine kinase 3 (FLT3) receptor, which is present in about 30% of CN-AML and confers a poor prognosis (1). FLT3 encodes a receptor tyrosine kinase expressed on hematopoietic progenitor cells involved in stem cell differentiation and proliferation (2). FLT3 activating mutations such as internal tandem duplication (ITD) lead to constitutive, ligand-independent activation of this receptor, conferring a growth and survival advantage. The mutation itself has not been shown to independently drive leukemic transformation in vivo (1,3). Rather, FLT3-ITD must collaborate with additional oncogenic mutations to trigger hematopoietic malignancy (3). Despite extensive research throughout the last decades, only Midastaurin has been recently approved by the FDA as a first line treatment in combination with chemotherapy (4) highlighting the difficulties for establishing targeted therapies. Therefore, novel approaches such as targeting downstream effectors of FLT3-ITD signaling are relevant to explore new therapeutic targets.