Variable prognostic value of FLT3 internal tandem duplications in patients with de novo AML and a normal karyotype, t(15;17), t(8;21) or inv(16).
BACKGROUND
Internal tandem duplication of the FLT3 gene (FLT3/ITD) has been linked to poor outcome in acute myeloid leukemia (AML). However, the prognostic value of FLT3/ITD in various cytogenetic risk groups is still a matter of debate. The aim of this study was to evaluate the prognostic significance in patients with de novo AML and a normal karyotype or a t(15;17), t(8;21) or inv(16) (good risk group).


METHODS
Diagnostic samples of 100 patients were investigated by single-step PCR of exons 11 and 12 of the FLT3 gene in a single center retrospective analysis. Subgroups included 53 patients with normal karyotype, 21 patients with t(15;17), 9 patients with t(8;21) and 17 patients with inv(16).


RESULTS
FLT3/ITD was found in 26 out of 100 patients: 30% of patients with a normal karyotype and 38% of t(15;17) patients tested positive. The complete remission (CR) rates for the ITD(+) or ITD(-) groups were 50 vs 76% in normal karyotypes, and 100 vs 53% in t(15;17) patients, while the relapse rates were 75 vs 25% in normal karyotypes and 50 vs 42% in t(15;17) patients. Overall survival (OS) and disease free survival (DFS) at 5 years were significantly different in patients with normal cytogenetics: ITD(+) vs ITD(-): OS 6 vs 28% (P<0.003); DFS 13 vs 41% (P<0.02) Interestingly, FLT3/ITD had no significant effect on the outcome of t(15;17) patients: ITD(+) vs ITD(-): OS 85 vs 53% (P=0.056), DFS 45 vs 60% (P=0.6) at 50 months.


CONCLUSIONS
These data suggest a high prognostic value of FLT3/ITD in patients with normal cytogenetics. However, we find no evidence that FLT3/ITD is a predictive marker for patients with t(15;17).
Kainz
Birgit
B
Division of Hematology, Department of Internal Medicine I, University of Vienna Medical School, Vienna, Austria.
Heintel
Daniel
D
Marculescu
Rodrig
R
Schwarzinger
Ilse
I
Sperr
Wolfgang
W
Le
Trang
T
Weltermann
Ansgar
A
Fonatsch
Christa
C
Haas
Oskar A
OA
Mannhalter
Christine
C
Lechner
Klaus
K
Jaeger
Ulrich
U
D000208:Acute Disease; D007446:Chromosome Inversion; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D002891:Chromosomes, Human, Pair 21; D005260:Female; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D020080:Tandem Repeat Sequences; D014178:Translocation, Genetic; D051941:fms-Like Tyrosine Kinase 3
D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3