Incidence and prognostic value of FLT3 internal tandem duplication and D835 mutations in acute myeloid leukemia.
OBJECTIVE
Cytogenetics is the most important prognostic factor in acute myeloid leukemia (AML). However, a high proportion of patients show normal or intermediate-risk karyotypes. In these patients, other determinants could help to identify those with a higher risk of relapse. Recently, internal tandem duplications (ITD) and D835 mutations in FLT3 tyrosine kinase receptor have been shown to confer a bad prognosis in AML.


METHODS
We analyzed the incidence of these mutations in a total of 208 patients of different AML subsets and their prognostic relevance in non-promyelocytic de novo AML.


RESULTS
FLT3 mutations were detected in 24% of de novo AML, 42% of acute promyelocytic leukemia (APL) and 17% of secondary AML. Four patients showed both ITD and D835 mutations. Ninety-four per cent of the patients with FLT3 alterations were classified into the intermediate-risk group. There was no association between the presence of FLT3 alterations and response to induction while the alterations were associated with a worse disease-free survival and event-free survival in both the overall and intermediate-risk patients.


CONCLUSIONS
Our data confirm that any of the mutations in FLT3 confer a bad prognosis in AML. Because of the high prevalence of these mutations within the intermediate-risk group, their detection could be useful to identify patients with a poor prognosis.
Moreno
Isabel
I
Molecular Biology Laboratory (Dept. Medical Pathology), Hospital Universitario La Fe, Valencia, Spain.
Martín
Guillermo
G
Bolufer
Pascual
P
Barragán
Eva
E
Rueda
Eva
E
Román
José
J
Fernández
Pascual
P
León
Pilar
P
Mena
Armando
A
Cervera
José
J
Torres
Antonio
A
Sanz
Miguel A
MA
D000208:Acute Disease; D000328:Adult; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D015994:Incidence; D007951:Leukemia, Myeloid / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D020080:Tandem Repeat Sequences; 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