FLT3 inhibitor-induced neutrophilic dermatosis

Amir T. Fathi, Long Le, Robert P. Hasserjian, Hossein Sadrzadeh, Mark Levis, Yi Bin Chen

Research output: Contribution to journalArticlepeer-review

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 NPM1mutations 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.

Original languageEnglish (US)
Pages (from-to)239-242
Number of pages4
JournalBlood
Volume122
Issue number2
DOIs
StatePublished - Jul 11 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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