FLT3 internal tandem duplication in acute myeloid leukemia at diagnosis and relapse

R Hovland, PhD

Haukeland University Hospital, Bergen, Bergen Norway

Internal tandem duplication (ITD) of receptor tyrosine kinase FLT3 occurs in 20-30% of patients with AML. The length of the duplicated region and the location varies between the patients, but it is always in-frame and in the juxtamembrane domain of the tyrosine kinase. FLT3-ITD has been shown to be an important adverse prognostic factor independent of standard karyotype. Our aim was to study AML samples obtained at initial diagnosis and at relapse with respect to FLT3-ITD. METHODS: Exon 14 to 15 was amplified by genomic PCR. The PCR products were detected by ABI 310 genetic analyzer, which has a high sensitivity. FLT3-ITD was identified as fragments migrating above the expected 328-bp size of the wild-type. Abnormal sized fragments were sequenced. RESULTS: FLT3-ITD at diagnosis and relapse has so far only been analyzed in two patients, but none of these patients were found to have consistent FLT3-ITD. Pasient A showed a FLT3-ITD at relapse only. In patient B the duplicated region were different in the samples at diagnosis and relapse. CONCLUSIONS: Patient specific real-time PCRs assays for FLT3-ITD have been used to detect minimal residual disease. These data indicate that FLT3-ITD can not be trusted as a molecular marker of minimal residual disease.

KEY WORDS: leukemia, mutation.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Chromosomal Aberrations.