Immunophenotypic findings in acute myeloid leukemia with FLT3 internal tandem duplication.
OBJECTIVE
The biological characteristics and the prognostic significance of the internal tandem duplication of the FLT3 (FLT3/ITD) were investigated in a series of de novo acute myeloid leukemia (AML) patients. One hundred and fifty-six adult patients with AML were included in the study. FLT3/ITD was detected in 41 (26%) patients (FLT3/ITD(+)).


METHODS
The main differences observed between the groups with and without FLT3/ITD: a higher leukocyte count, a raised percentage of a normal karyotype and a more frequent M5 FAB diagnosis in the FLT3/ITD(+) patients. As regards the immunophenotype characteristics the FLT3/ITD(+) group very often expressed monocytic markers (CD36 and CD11b) and less commonly immature markers (CD34 and CD117). A promyelocytic-like immunophenotype pattern was also detected in a minority of these patients(4/36).


RESULTS
The FLT3/ITD(+) patients had a shorter overall survival, a shorter event-free survival and a higher probability of relapse. Minimal residual disease (MRD) was investigated in the FLT3/ITD(+) patients using flow cytometry. This technique had a sensitivity of 62% and a specificity of 83% in relapse prediction. Minimal residual disease analysis was hampered by the low number of patients with detectable aberrant immunophenotype.


CONCLUSIONS
A high frequency of changes in the phenotype and/or genotype pattern between diagnosis and relapse was detected (5/6). FLT3/ITD is a frequent molecular lesion in de novo adult AML and seems to be associated with a monocytic differentiation, a high leukocyte count and a poor prognosis. Immunophenotype and genotype patterns observed at relapse suggest that the FLT3/ITD(+) blasts may be genetically unstable and prone to clonal evolution. FLT3/ITD may not be a suitable target for minimal residual disease studies.
Muñoz
Luz
L
Laboratori d'Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Aventín
Ana
A
Villamor
Neus
N
Juncà
Jordi
J
Acebedo
Gemma
G
Domingo
Alicia
A
Rozman
María
M
Torres
J Pio
JP
Tormo
Mar
M
Nomdedéu
Josep F
JF
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3
D015703:Antigens, CD; D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3