Distinct immunophenotype of early T-cell progenitors in T lymphoblastic leukemia/lymphoma may predict FMS-like tyrosine kinase 3 mutations

FMS-like tyrosine kinase 3 (FLT3) mutation in T lymphoblastic leukemia/lymphoma (T-LL) is rare (∼4%) and reported only in cases with CD117 expression. This study aimed to identify the immunophenotypic features that may predict FLT3 mutations. We report 3 (43%) of 7 CD117 ⁺ T-LL cases harboring FLT3-internal tandem duplication mutation. Compared with 4 FLT3-unmutated cases, all 3 FLT3-mutated cases had a distinct immunophenotype (CD1a ^-/CD2 ⁺/CD7 ⁺/CD34 ⁺/CD117 ^uniform+/Tdt ⁺) corresponding to the stage of earliest thymic T-cell progenitors possessing myeloid lineage potential. Indeed, all FLT3-mutated T-LL cases expressed myeloperoxidase on a very small subset of blasts and, thus, may be further considered a mixed phenotype acute leukemia, T/myeloid, by the 2008 World Health Organization classification scheme. We conclude that this unique immunophenotype (CD1a ^-/CD2 ⁺/CD7 ⁺/CD34 ⁺/CD117 ⁺/Tdt ⁺) is a better predictor of FLT3 mutation than sole CD117 expression.