Clusters of activating deletions in the FLT-3 JMD. (A) Distribution of FLT-3 deletions as reported in the COSMIC database (query performed on 9 August 2017). The shaded regions indicate 2 enrichment clusters of deletions in the JMD and at the canonical TKD sites (D835/I836). (B) Permutation analysis of the distribution of mutated residues demonstrates significant enrichment of the expected ITD and TKD regions (both off scale). The frequency of mutation of each residue, as reported, is plotted. Shading indicates levels of significance compared with the predicted distributions (1 × 10⁵ resamplings). The inset shows the same analysis but examines the deletions only. The entire CDS was analyzed, but only the JMD is plotted; the TKD was also enriched for deletions as expected. (C) Scheme for identifying activating mutations within the K568-V581 cluster. (D) Photographs of the MTT assay plates for cells expressing the different FLT-3 constructs in the presence (right) and absence (left) of rm IL-3, after 5 days. Relevant clones are indicated.