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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-01-0195.
Submitted January 24, 2002
Accepted May 15, 2002
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
Division of Hematology-Oncology, Chang Gung Memorial Hospital, Taipei, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
Division of Hematology-Oncology, Chang Gung Memorial Hospital, Taipei, Taiwan
* Corresponding author; email: sly7012{at}adm.cgmh.org.tw.
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, while 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% vs. 17.9±3.6%, (P<0.001). 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=0.777). 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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