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Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias
Ist Teil von
Leukemia, 2011-07, Vol.25 (7), p.1147-1152
Ort / Verlag
London: Nature Publishing Group UK
Erscheinungsjahr
2011
Quelle
MEDLINE
Beschreibungen/Notizen
The impact of
ten-eleven-translocation 2 (TET2)
mutations on response to azacitidine (AZA) in MDS has not been reported. We sequenced the
TET2
gene in 86 MDS and acute myeloid leukemia (AML) with 20–30% blasts treated by AZA, that is disease categories wherein this drug is approved by Food and Drug Administration (FDA). Thirteen patients (15%) carried
TET2
mutations. Patients with mutated and wild-type (WT)
TET2
had mostly comparable pretreatment characteristics, except for lower hemoglobin, better cytogenetic risk and longer MDS duration before AZA in
TET2
mutated patients (
P
=0.03,
P
=0.047 and
P
=0.048, respectively). The response rate (including hematological improvement) was 82% in MUT versus 45% in WT patients (
P
=0.007). Mutated
TET2
(
P
=0.04) and favorable cytogenetic risk (intermediate risk:
P
=0.04, poor risk:
P
=0.048 compared with good risk) independently predicted a higher response rate. Response duration and overall survival were, however, comparable in the MUT and WT groups. In higher risk MDS and AML with low blast count,
TET2
status may be a genetic predictor of response to AZA, independently of karyotype.