Distinct Immunophenotype of Early T-Cell Progenitors in T Lymphoblastic Leukemia/Lymphoma May Predict for FLT3 Mutations.
Charles Zaremba, Dwight Oliver, MaryEllen Cavalier, Franklin Fuda, Nitin Karandikar, Weina Chen. UT Southwestern Medical Center, Dallas
Background: FLT3 mutation in T lymphoblastic leukemia/lymphoma (T-LL) has been reported only in 6 cases and all with CD117 expression (Blood 104: 558 and 106:4414). As the FLT3 mutation is rare (∼4% in T-LL), testing all T-LL cases for this mutation may be unnecessary. This study aimed to identify immunophenotypic features that may predict FLT3 mutations.
Design: Searching a 4-color flow cytometry database (2006 to 2010) yielded 36 cases of T-LL. Seven (19%) cases demonstrated CD117 expression. Of these, 5 cases were studied for FLT3 mutation by polymerase-chain reaction (PCR) with fragment analysis. Two cases were positive (∼ 40%). An additional 6 reported T-LL cases studied for FLT3 mutations in the literature were included in the analysis.
Results: There were 7 FLT3-mutated cases [age 6-55 years, 1 female (F) and 4 males (M)] and 4 FLT3-wild type cases (age 7-75 years, 1F and 3M). There were no age and gender differences between the two groups. Six patients had FLT3 internal tandem duplication and one had a point mutation (D835Y). All FLT3-mutated cases had a distinct immunophenotype characterized by co-expression of CD2, CD7, CD34, TdT, CD117(uniformly positive) and lack of CD1a expression (7/7 vs. 0/4 in wild type cases, p<0.01). This immunophenotype resembles early T-cell progenitors retaining myeloid potential. Indeed, 4 cases expressed MPO on a small subset of blasts and thus could be further classified as mixed phenotype acute leukemia, T/myeloid by the 2008 WHO scheme. Unlike the FLT3-mutated cases, the FLT-3-wild type cases demonstrated partial expression of CD117. Expression profiles for the following markers were similar in the two groups (positive/tested cases in 2 groups): surface CD3 (1/11), intracellular CD3 (11/11), CD4 (2/11), CD5 (5/11), CD8 (1/11), CD10 (1/8), CD13/CD33 (9/11).
Conclusions: This study confirms a low incidence of FLT3 mutation in T-LL. Remarkably, these cases exhibit a distinct immuophenotype resembling early T-cell progenitors retaining myeloid potential, characterized by co-expression of CD34, TdT and CD117, which should prompt studies for FLT3 mutations. Our results thus identify a subset of T-LL patients that may benefit from therapeutic intervention with FLT3 inhibitor, and suggest that FLT3 mutations may play a role in oncogenesis.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 155, Wednesday Morning