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, Nancy
Hählen, K
Reinhardt, D
Creutzig, U
Schuurhuis, G J
Zwaan, Ch M
Kaspers, G J L #
Issue Date: Jul-2006
Series Title: Leukemia vol:20 issue:7 pages:1217-20
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.
ISSN: 0887-6924
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Clinical Bacteriology and Mycology
Department of Oncology - miscellaneous
× corresponding author
# (joint) last author

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