FLT3 Length Mutations as Marker for Follow-Up Studies in Acute Myeloid Leukaemia

Length mutations within the FLT3 gene (FLT3-LM) can be found in 23%
of acute myeloid leukaemia (AML) and thus are the most frequent
mutations in AML. FLT3-LM are highly correlated with AML with
normal karyotype and other cytogenetic aberrations of the
prognostically intermediate group. This group is supposed to be a
mixed group of AML with differences in the underlying pathogenesis.
For more individualized treatment options it would be helpful to
better characterize this large AML group not only by molecular
mutations but also use these markers for the definition of minimal
residual disease (MRD). However, so far the cytogenetically
intermediate AML has been lacking suitable markers for PCR-based
MRD detection like the fusion genes in the prognostically
favourable subgroups. The suitability of the FLT3-LM as a target
for PCR-based MRD was discussed controversially as it seemed to be
a rather unstable marker. Thus, we aimed at the evaluation of
FLT3-LM as a marker for residual disease in a large cohort of AML.
Paired samples of 97 patients with AML at diagnosis and at relapse
were analyzed. It could be shown that in only four cases a loss of
the length mutation was detected. This is in the range of other
well-characterized AML relapsing with a different geno- and/or
phenotype. In contrast, a change in the ratio of the mutated allele
in comparison to the wild-type allele was frequently observed. In
detail, the FLT3-LM showed a tendency to accumulate during disease
progression and was found more frequently at relapse than at
diagnosis. In addition, 45 patients were analyzed at different time
points during and after therapy. Using conventional PCR it clearly
could be shown that for most of the patients positive at
presentation FLT3-LM is a reliable PCR marker for monitoring
treatment response. Even an early detection of relapse was possible
in some cases. Copyright (C) 2004 S. Karger AG, Basel.