Details

Autor(en) / Beteiligte

• Chillón, M C
• Gómez-Casares, M T
• López-Jorge, C E
• Rodriguez-Medina, C
• Molines, A
• Sarasquete, M E
• Alcoceba, M
• Miguel, J D G-S
• Bueno, C
• Montes, R
• Ramos, F
• Rodríguez, J N
• Giraldo, P
• Ramírez, M
• García-Delgado, R
• Fuster, J L
• González-Díaz, M
• Menendez, P

Titel

Prognostic significance of FLT3 mutational status and expression levels in MLL-AF4+ and MLL-germline acute lymphoblastic leukemia

Ist Teil von

• Leukemia, 2012-11, Vol.26 (11), p.2360-2366

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• There is barely any information about the prognostic significance of FLT3 expression and mutational status in cytogenetically distinct subgroups of acute lymphoblastic leukemia (ALL). We analyzed the presence of FLT3-tyrosine kinase domain (TKD) and FLT3-internal tandem duplication (ITD) mutations as well as FLT3 expression levels in 54 newly diagnosed patients with B-ALL ( n =49) or T-ALL ( n =5). All B/T-ALL samples tested negative for the presence of FLT3-TKD or FLT3-ITD. None of the T-ALL and E2A-PBX1+ B-ALL overexpressed FLT3 . In contrast, mainly MLL-AF4+ B-ALL but also ETV6-RUNX1+, BCR-ABL+ or B-ALL displaying normal cytogenetics exhibited significantly higher FLT3 expression levels than normal bone marrow, supporting that aberrantly increased transcription of FLT3 , rather than activating FLT3 mutations, contributes to the pathogenesis of these B-ALL. Using the median FLT3 expression as cut-off value we found that high-level FLT3 expression is associated with an extremely poor 1-year overall survival (OS; 0 vs 71%; P =0.002) and disease-free survival (DFS; 0 vs 43%; P =0.03) in MLL-AF4+ B-ALL but not in MLL-germline B-ALL. Cox regression analysis with OS/DFS as end points showed that age>14 years and high-level FLT3 expression were independent prognostic factors when all ALL patients were analyzed together. Importantly, when the MLL-AF4+ B-ALL subgroup was analyzed separately, high-level FLT3 expression was the only independent prognostic factor for OS and treatment outcome. These findings indicate that high FLT3 expression identifies MLL-AF4+ ALL patients at very high risk of treatment failure and poor survival, emphasizing the value of ongoing/future clinical trials for FLT3 inhibitors.