CD123 Immunohistochemical Expression in Acute Myeloid Leukemia Is Associated with FLT3-ITD but Not NPM1 Mutations
Marian A Rollins-Raval, Raju K Pillai, Miroslav Djokic, Jeffrey A Kant, Christine G Roth. University of Pittsburgh School of Medicine, Pittsburgh, PA
Background: Expression of interleukin-3 receptor alpha chain CD123 may be seen in hematologic malignancies including leukemic blasts. Prior flow cytometric studies have suggested that CD123 positivity in acute myeloid leukemia (AML) may be linked to fms-related tyrosine kinase 3 internal tandem duplications (FLT3-ITD) and/or nucleophosmin (NPM1) mutations. Immunohistochemical (IHC) studies performed on bone marrow biopsies or clot/particle preparations may be useful to characterize AML, especially in cases lacking adequate aspirate material. The aim of this study was to define clinicopathologic features of CD123 IHC+ AML and correlate with FLT3-ITD and NPM1 mutation status.
Design: 67 newly diagnosed AML with NPM1 and/or FLT3-ITD mutation analysis were identified in our pathology archives and analyzed with CD123 IHC (9F5 clone, BD Pharmingen). FLT3-ITD & NPM1 molecular analyses were performed at diagnosis using PCR with fluorescent-labeled primers followed by capillary electrophoresis/Genescan analysis to distinguish wild-type & mutant alleles. CD123 IHC was correlated with the clinical & pathologic features, including cytogenetic risk group stratification & overall survival.
Results: 40%(27/67) of AML were CD123 IHC+. There was no significant difference of CD123 IHC status for median age or male:female ratio. CD123 IHC+ AML was comprised of 19 (70%) AML not otherwise specified (NOS), 4 (15%) with recurrent genetic abnormalities, 3 (11%) therapy-related, & 1 (4%) with myelodysplasia-related changes (MRC). CD123 IHC- AML was comprised of 22 (55%) AML NOS, 9(22.5%) with recurrent genetic abnormalities, 7 (17.5%) AML-MRC, & 2 (5%) therapy-related. Of CD123 IHC+ AML, 12% (3/26) showed favorable cytogenetics, 77% (20/26) showed intermediate cytogenetics, and 12% (3/26) showed adverse cytogenetics, which did not differ significantly from CD123 IHC- AML. 77% (13/17) FLT3-ITD-mutated vs. 8% (4/48) FLT3-ITD-wild-type cases were CD123 IHC+ (P=0.0005). 54% (13/24) NPM1-mutated vs. 30% (11/37) NPM1-wild-type cases were CD123 IHC+ (P>0.05). CD123 IHC+ AML showed a trend toward shorter overall survival as compared to CD123 IHC- AML (median=23.8 vs. 28.75 months), but the difference was not significant.
Conclusions: CD123 IHC positivity in AML is significantly associated with FLT3-ITD mutations and may be useful to direct additional ancillary testing on peripheral blood or other involved specimens in cases lacking adequate aspirate material. NPM1 mutation and other clinicopathologic variables do not significantly differ by CD123 IHC status.
Monday, March 19, 2012 2:15 PM
Platform Session: Section C, Monday Afternoon