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Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples.

Authors: Cloos, J  Goemans, BF  Hess, CJ  Van Oostveen, JW  Waisfisz, Q  Corthals, S  De Lange, D  Boeckx, N  Hahlen, K  Reinhardt, D  Creutzig, U  Schuurhuis, GJ  Zwaan, CHM  Kaspers, GJ 
Citation: Cloos J, etal., Leukemia. 2006 Jul;20(7):1217-20. Epub 2006 Apr 27.
Pubmed: (View Article at PubMed) PMID:16642044
DOI: Full-text: DOI:10.1038/sj.leu.2404246

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.


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CRRD Object Information
CRRD ID: 11049467
Created: 2016-04-06
Species: All species
Last Modified: 2016-04-06
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.