FLT3 inhibitor-induced neutrophilic dermatosis

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

Research output: Contribution to journalArticle

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

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Skin Diseases
Protein-Tyrosine Kinases
Granulocyte Precursor Cells
Skin
Fluorescence In Situ Hybridization
Acute Myeloid Leukemia
Neutrophils
Fluorescence
Clinical Trials
Mutation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Fathi, A. T., Le, L., Hasserjian, R. P., Sadrzadeh, H., Levis, M. J., & Chen, Y. B. (2013). FLT3 inhibitor-induced neutrophilic dermatosis. Blood, 122(2), 239-242. https://doi.org/10.1182/blood-2013-01-478172

FLT3 inhibitor-induced neutrophilic dermatosis. / Fathi, Amir T.; Le, Long; Hasserjian, Robert P.; Sadrzadeh, Hossein; Levis, Mark J; Chen, Yi Bin.

In: Blood, Vol. 122, No. 2, 11.07.2013, p. 239-242.

Research output: Contribution to journalArticle

Fathi, AT, Le, L, Hasserjian, RP, Sadrzadeh, H, Levis, MJ & Chen, YB 2013, 'FLT3 inhibitor-induced neutrophilic dermatosis', Blood, vol. 122, no. 2, pp. 239-242. https://doi.org/10.1182/blood-2013-01-478172
Fathi AT, Le L, Hasserjian RP, Sadrzadeh H, Levis MJ, Chen YB. FLT3 inhibitor-induced neutrophilic dermatosis. Blood. 2013 Jul 11;122(2):239-242. https://doi.org/10.1182/blood-2013-01-478172
Fathi, Amir T. ; Le, Long ; Hasserjian, Robert P. ; Sadrzadeh, Hossein ; Levis, Mark J ; Chen, Yi Bin. / FLT3 inhibitor-induced neutrophilic dermatosis. In: Blood. 2013 ; Vol. 122, No. 2. pp. 239-242.
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