FLT3 Mutation Is Rare in T Lymphoblastic Leukemia (ALL) and Its Presence Supports Concurrent Myeloid Differentiation.
Daniela Hoehn, Yasin Ahmed, Su S Chen, Tian Tian, L Jeffrey Medeiros, Pei Lin. University of Texas M.D. Anderson Cancer Center, Houston; St. John Hospital and Medical Center, Detroit, MI
Background: Others have reported FLT3 mutation in a small subset of T-ALL cases that express CD117 (Paietta et al. Blood 104: 558, 2004). To better understand these neoplasms, we reviewed our experience with cases of T-ALL and biphenotypic T/myeloid leukemia evaluated for FLT3 mutations.
Design: We retrospectively searched our files for T-ALL and T/myeloid leukemia cases, analyzed for FLT3 mutations as part of the routine clinical workup. The diagnosis of T-ALL or biphenotypc T/myeloid leukemia was established based on multicolor flow cytometric immunophenotyping and MPO reactivity by cytochemical stain on bone marrow aspirate smears. FLT3 mutations were detected by PCR and capillary electrophoresis. Clonality of the T-cell receptor (TCR) γ and β chain genes was assessed by PCR.
Results: We identified 21 T-ALL and 23 T/myeloid leukemia cases. FLT3 mutation was identified in 8 cases: 7 internal tandem duplications, 1 D835 point mutation. The 8 cases were classified as 7 T/myeloid leukemia and 1 T-ALL. Each mutated case was positive for CD117, CD34, CD13, CD7 and TdT. Other T-cell and myeloid antigens expressed were CD2 (7/8), cytoplasmic CD3 (7/8), CD5 (4/8), CD15 (4/6) and CD33 (4/8). The 7 T/myeloid leukemia cases expressed MPO. Monoclonal TCR gene rearrangement was detected only in the T-ALL case and none of the 5 T/myeloid cases analyzed. To determine if CD117 predicts FLT3 mutation status, we specifically reviewed the CD117 data in this cohort. Seven of 21 (33%) T-ALL and 17 of 23 (74%) T/myeloid leukemia expressed CD117.
|T cell/lymphoid markers||Myeloid/stem cell markers||MPO (%)||FLT3|
|1||CD2, cCD3, CD7, TdT||CD13, CD34, CD117||10||ITD|
|2||CD2, cCD3, CD5, CD7, TdT||CD13, CD15, CD34, CD117||2||ITD|
|3||CD2,cCD3, CD5, TdT||CD13, CD15, CD33, CD34, CD117||6||ITD|
|4||CD2, CD5, CD7, CD10, TdT||CD13, CD33, CD34, CD117||50||D835|
|5||CD2, cCD3, CD5, CD7, TdT||CD13, CD15, CD34, CD117||5||ITD|
|6||CD2, cCD3, CD7, TdT||CD13, CD15, CD33, CD34, CD117||9||ITD|
|7||CD2, cCD3, CD7, TdT||CD13, CD34, CD117||3||ITD|
|8||cCD3, CD5, CD7, CD10, TdT||CD13, CD33, CD34, CD117||Neg||ITD|