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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-01-0195.
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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2387-2392
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Internal tandem duplication of FLT3 in relapsed acute
myeloid leukemia: a comparative analysis of bone marrow samples
from 108 adult patients at diagnosis and relapse
Lee-Yung Shih,
Chein-Fuang Huang,
Jin-Hou Wu,
Tung-Liang Lin,
Po Dunn,
Po-Nan Wang,
Ming-Chung Kuo,
Chang-Liang Lai, and
Hui-Chin Hsu
From the Division of Hematology-Oncology, Department of
Internal Medicine, Chang Gung Memorial Hospital, and Chang Gung
University, Taipei, Taiwan.
Analysis of internal tandem duplications of FLT3
(FLT3/ITD) was performed on bone marrow samples obtained at
diagnosis and relapse from 108 adult patients with de novo acute
myeloid leukemia (AML) to determine the role of this mutation in
leukemic relapse. Eighty-three patients had wild-type FLT3
at both diagnosis and relapse, 16 had FLT3/ITD at both
stages, whereas 8 had acquired the mutation and 1 had lost it at
relapse. Using Genescan analysis, we found that FLT3/ITD
levels at first relapse were significantly higher than those at
diagnosis (mean ± SE, 40.5% ± 4.8% versus 17.9% ± 3.6%,
P < .001). The increase in mutation levels at relapse as
compared with diagnosis did not correlate with the difference in blast
cell percentages at both stages (P = .777). A hemizygous deletion of wild-type FLT3 was found in 4 patients at
relapse compared to none at diagnosis. Nine of the 11 patients carrying a single mutation at diagnosis relapsed with an identical mutation. All
6 patients with more than one FLT3/ITD mutation at
diagnosis showed changes in mutation patterns and levels at first
relapse; however, each patient retained at least one mutation in the
relapse sample. The changes of mutation patterns had implications for the monitoring of minimal residual disease. Our results suggest that
FLT3/ITD may contribute as the initial transforming event in AML, and relapse can reflect the selection and outgrowth of a mutant
clone or evolution of a new clone harboring this mutation.
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