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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-02-0420.
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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2393-2398
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Studies of FLT3 mutations in paired presentation and
relapse samples from patients with acute myeloid leukemia: implications
for the role of FLT3 mutations in leukemogenesis, minimal
residual disease detection, and possible therapy with FLT3
inhibitors
Panagiotis D. Kottaridis,
Rosemary E. Gale,
Stephen E. Langabeer,
Marion E. Frew,
David T. Bowen, and
David C. Linch
From the Department of Haematology, University
College London, London, United Kingdom; and the Department of Molecular
and Cellular Pathology, Ninewells Hospital, Dundee, United Kingdom.
FLT3 mutations, either internal tandem duplications
(ITDs) or aspartate residue 835 (D835) point mutations, are present in approximately one third of patients with acute myeloid leukemia (AML)
and have been associated with an increased relapse rate. We have
studied FLT3 mutations in paired presentation and relapse samples to ascertain the biology of these mutations and to evaluate whether they can be used as markers of minimal residual disease. At
diagnosis, 24 patients were wild-type FLT3, and 4 acquired a FLT3 mutation at relapse (2 D835+, 2 ITD+), with a further patient acquiring an ITD at second
relapse. Of 20 patients positive at diagnosis (18 ITD+, 2 D835+), 5 who were all originally ITD+ had no
detectable mutation at relapse, as determined by a sensitive radioactive polymerase chain reaction. One of these patients had acquired an N-Ras mutation not detectable at presentation.
Furthermore, another patient had a completely different ITD at relapse,
which could not be detected in the presentation sample. These results indicate that FLT3 mutations are secondary events in
leukemogenesis, are unstable, and thus should be used
cautiously for the detection of minimal residual disease.
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