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- Title
Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples.
- Authors
Cloos, J; Goemans, B F; Hess, C J; van Oostveen, J W; Waisfisz, Q; Corthals, S; de Lange, D; Boeckx, N; Hählen, K; Reinhardt, D; Creutzig, U; Schuurhuis, G J; Zwaan, Ch M; Kaspers, G J L
- Abstract
In acute myeloid leukemia (AML), activating mutations in the fms-like tyrosine kinase 3 (FLT3) gene predict poor prognosis. We determined FLT3 internal tandem duplications (FLT3/ITD) and D835 point mutations in paired initial and relapse samples from 80 pediatric and adult AML patients. One D835 point mutation was found in an initial pediatric AML sample. Fms-like tyrosine kinase 3/ITDs were present in 21 initial and 22 relapse samples (26.3 and 27.5%, respectively). Interestingly, FLT3/ITD positivity was related to a significantly shorter time to relapse, most pronounced when the ITD-positive status was found at relapse (P<0.001). However, FLT3/ITD status changed between diagnosis and relapse in 14 cases. In four patients, the FLT3/ITD became undetectable at relapse in five patients FLT3/ITDs were only detected at relapse, and in five patients the length or number of FLT3/ITDs changed. Gain of FLT3/ITDs may suggest oligoclonality with selective outgrowth of the FLT3/ITD-positive clone, whereas losses may reflect ITDs in the more mature leukemic cells rather than in the leukemic stem cell, or, alternatively, that other genetic aberrations provided a greater selective advantage. Studying FLT3/ITD kinetics in minimal residual disease setting may provide some answers for the changes we observed. Fms-like tyrosine kinase 3/ITD is a relevant marker for prognosis, and remains an important target for therapeutic inhibition.Leukemia (2006) 20, 1217–1220. doi:10.1038/sj.leu.2404246; published online 27 April 2006
- Subjects
MYELOID leukemia; BONE marrow diseases; PROTEIN-tyrosine kinases; CANCER diagnosis; THERAPEUTICS
- Publication
Leukemia (08876924), 2006, Vol 20, Issue 7, p1217
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/sj.leu.2404246