CD123 Immunohistochemical expression in acute myeloid leukemia is associated with underlying FLT3-ITD and NPM1 mutations

Marian Rollins-Raval, Raju Pillai, Katsuhiko Warita, Tomoko Mitsuhashi-Warita, Rohtesh Mehta, Michael Boyiadzis, Miroslav Djokic, Jeffrey A. Kant, Christine G. Roth

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31 Scopus citations


FLT3-ITD and NPM1 mutation testing in acute myeloid leukemia (AML) plays an important role in prognostic risk stratification, especially within the intermediate cytogenetic risk group. Molecular studies require adequate fresh material and are typically performed on a dedicated aspirate specimen, which may not be available in all cases. Prior flow cytometric studies have suggested an association between CD123 overexpression in AML and FLT3-ITD and/or NPM1 mutations; however, the immunohistochemical (IHC) correlate is unknown. We assessed CD123 IHC expression in 157 AML bone marrow biopsies and/or marrow particle preparations, and correlated with the morphologic, immunophenotypic, and cytogenetic features and with the presence of FLT3-ITD and NPM1 mutations. We found that CD123 IHC expression, seen in 40% of AML, occurred across a wide spectrum of 2008 World Health Organization subtypes and was most frequent within the intermediate risk group. As compared with CD123 IHC-AML, CD123 IHC+AML demonstrated higher marrow blast percentages (median 69%), monocytic differentiation (33/63 cases), and CD34 negativity (29/63 cases). Eighty-three percent (25/30) FLT3-ITD-mutated AML were CD123+ (P<0.0001) and 62% (18/29) NPM1-mutated cases were CD123 IHC+ (P=0.0052) with negative predictive values of 95% for FLT3-ITD and 88% for NPM1. CD123 IHC+AML presents with characteristic pathologic features, some of which may be related to underlying FLT3-ITD and/or NPM1 mutations.

Original languageEnglish (US)
Pages (from-to)212-217
Number of pages6
JournalApplied Immunohistochemistry and Molecular Morphology
Issue number3
StatePublished - May 1 2013


  • CD123
  • FLT3-ITD
  • NPM1
  • acute myeloid leukemia
  • immunohistochemistry


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