FLT3 mutations are observed in 24.3% of AML (COSMIC). Of these, most are internal tandem duplications. FLT3 internal tandem duplication (ITD) occurs when sequences of less than ten to several hundred bases in length are repeated within the juxtamembrane domain (Fathi and Chen 2011; Kottaridis et al. 2001). All duplications are “in frame,” with the number of nucleotides added as a multiple of three. Corresponding new amino acids are inserted into the protein, but the coding frame of the protein remains unchanged. In addition to internal tandem duplications, point mutations have also been observed in the tyrosine kinase domain (TKD) of the FLT3 protein in 5-7% of AML patients. FLT3 ITD and FLT3 TKD mutations lead to aberrant activation of FLT3 signaling, leading to proliferation of tumor cells (Leung, Man, and Kwong 2013). FLT3 mutations fall into class I of the “two-hit” theory of leukemogenesis (Naoe and Kiyoi 2013).​