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Detection of Flt3-internal tandem duplication (ITD) in acute myelogenous leukemia (AML) blasts at the time of diagnosis is associated with an increased risk of leukemia relapse after chemotherapy. In the present report, we describe two patients with Flt3-abnormalities that were only detectable at the time of relapse. One of the patients had an ITD at the time of diagnosis (duplicated region 41-133 numbered from the start of exon 14 plus CGG insertion), but at the time of relapse a new abnormality (duplicated region 70-230 plus insertion GGGGAGT) was detected as the only Flt3-abnormality. The second patient showed no Flt3-ITD at the time of diagnosis, but ITD was detected at the time of relapse (duplicated region 12-96, no insertion). Our observations of independent Flt3-ITD and the detection of new Flt3-abnormalities at the time of relapse suggest that (i) Flt3-gene abnormalities may be even more important in the pathogenesis of chemotherapy-resistant AML than suggested from previous studies of newly diagnosed AML, and (ii) monitoring of minimal residual disease by using patient-specific real-time polymerase chain reaction assays for Flt3-abnormalities may not be reliable.
Hovland et al. (2002) studied this question.