A patient on hydroxyurea for sickle cell disease who developed an opportunistic infection

We were interested in the recent report by Kelly et al 1 that FLT3 internal tandem duplication (FLT3-ITD) mutations, while sufficient to induce a chronic myeloproliferative disease in a murine bone marrow transplant (BMT) assay, were not sufficient to induce an acute myeloid leukemia (AML) phenotype. These data suggest that FLT3-ITDs may require additional cooperating mutations to generate the AML phenotype. The animals developed a leukocytosis, a hyperplastic bone marrow with significant reticulin fibrosis and marked splenomegaly. The authors suggested that it would be worthwhile to investigate chronic myeloproliferative syndromes, including myeloid metaplasia with fibrosis, for the presence of activating mutations in FLT3. We report here our findings from the study of FLT3-ITD mutations in 40 patients with agnogenic myeloid metaplasia (AMM).