title: 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.
abstract: 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.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, and Chang Gung University, Taipei, Taiwan. sly7012@adm.cgmh.org.tw
authors.forename: Lee-Yung
authors.initials: LY
authors.lastname: Shih
authors.forename: Chein-Fuang
authors.initials: CF
authors.lastname: Huang
authors.forename: Jin-Hou
authors.initials: JH
authors.lastname: Wu
authors.forename: Tung-Liang
authors.initials: TL
authors.lastname: Lin
authors.forename: Po
authors.initials: P
authors.lastname: Dunn
authors.forename: Po-Nan
authors.initials: PN
authors.lastname: Wang
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Kuo
authors.forename: Chang-Liang
authors.initials: CL
authors.lastname: Lai
authors.forename: Hui-Chin
authors.initials: HC
authors.lastname: Hsu
mesh_terms: D000328:Adult; D001752:Blast Crisis / Q000235:genetics; D001853:Bone Marrow / Q000473:pathology*; D002869:Chromosome Aberrations; D005260:Female; D020440:Gene Duplication; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012008:Recurrence; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051941:fms-Like Tyrosine Kinase 3
chemical_list: D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3