Terminal Deoxynucleotidyl Transferase (TdT) Flow Cytometric (FC) Expression in Acute Myeloid Leukemia (AML) Is Associated with CD34 Positivity, Lack of NPM1 Mutation, and Adverse Cytogenetic Risk Stratification
Rashi L Singhal, Nidhi Aggarwal, Stephen P Ten Eyck, Michael Boyiadzis, Christine G Roth, Miroslav Djokic. University of Pittsburgh School of Medicine, Pittsburgh, PA
Background: A subset of AML shows TdT expression, but the prognostic implications remain unclear in the current era, in part due to the reliance on maturation-related classification in prior studies. The aim of this study was to define clinicopathologic features of TdT+ AML classified by 2008 World Health Organization (WHO) criteria & correlate with molecular & cytogenetic abnormalities.
Design: 222 newly diagnosed AML cases with comprehensive FC data were identified in our pathology archives and classified per 2008 WHO criteria. TdT positivity in leukemic blasts was identified by FC. The results were correlated with clinicopathologic features, including age, sex, blast count, CD34, NPM1 & FLT3-ITD mutation status, karyotype, cytogenetic risk group stratification, & overall survival.
Results: 22% (48/222) of AML cases were TdT+. There was no significant difference in overall WHO 2008 diagnostic subclassification between TdT+ and TdT- AML.
98% (47/48) TdT+ AML were CD34+ versus (vs) 57% (100/174) TdT- AML (p<0.0001). 3% (1/34) NPM1-mutated (mut) vs 23% (30/131) NPM1-wild type (wt) AML were TdT+ (p=0.006). 24% (8/34) FLT3-ITD-mut AML vs 19% (25/135) FLT3-ITD-wt were TdT+ (p=0.4793). TdT+ AML more frequently fell into the adverse cytogenetic risk group as compared to TdT- AML (p=0.0206).
|Cytogenetic Risk Group Stratification||TdT+ AML||TdT- AML|
|Favorable Cytogenetics||2/45 (4%)||30/173 (17%)|
|Intermediate Cytogenetics||25/45 (56%)||105/173 (61%)|
|Adverse Cytogenetics||18/45 (40%) p=0.0206||38/173 (22%)|