title: FLT3 inhibitor-induced neutrophilic dermatosis.
abstract: The FLT3-ITD mutation is associated with poor outcomes in acute myeloid leukemia. Multiple FMS-like tyrosine kinase 3 (FLT3)-inhibitors have been studied in clinical trials. Recently, potent FLT3 inhibition was shown to induce terminal differentiation of FLT3-mutant myeloblasts. In 3 patients who developed characteristic skin nodules on initiation of FLT3-inhibition, we conducted dermatopathologic evaluation of skin samples, as well as FLT3 and NPM1 mutational analysis and fluorescence in situ hybridization. All 3 patients demonstrated characteristically deep dermal and subcutaneous neutrophilic infiltrates without evidence of myeloblasts. Discovery of FLT3-ITD and NPM1 mutations in 2 of the samples, as well as the presence of FLT3-ITD and deletion of 7q in the other, confirmed the ancestry of the differentiated neutrophils as that of the original FLT3-mutant myeloblasts. FLT3 inhibition can lead to clinically distinct dermatoses, which suggests the effect of FLT3 inhibition on myeloid differentiation and a manifestation of a broader "syndrome" associated with this therapy.
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA. afathi@partners.org.
authors.forename: Amir T
authors.initials: AT
authors.lastname: Fathi
authors.forename: Long
authors.initials: L
authors.lastname: Le
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hasserjian
authors.forename: Hossein
authors.initials: H
authors.lastname: Sadrzadeh
authors.forename: Mark
authors.initials: M
authors.lastname: Levis
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
mesh_terms: D000328:Adult; D001706:Biopsy; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020556:Neutrophil Infiltration; D000090243:Nucleophosmin; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology*; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: C000716967:NPM1 protein, human; D047428:Protein Kinase Inhibitors; D000090243:Nucleophosmin; D051941:fms-Like Tyrosine Kinase 3