NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS).
Mutations in the NPM1 gene represent the most frequent genetic alterations in patients with acute myeloid leukemia (AML) and are associated with a favorable outcome. In 690 normal karyotype (NK) AML patients the complete remission rates (CRs) and the percentage of patients with adequate in vivo blast cell reduction 1 week after the end of the first induction cycle were significantly higher in NPM1(+) (75% and 80%, respectively) than in NPM1(-) (57% and 57%, respectively) patients, but were unaffected by the FLT3-ITD status. Multivariate analyses revealed the presence of a NPM1 mutation as an independent positive prognostic factor for the achievement of an adequate day-16 blast clearance and a CR. In conclusion, NPM1(+) blast cells show a high in vivo sensitivity toward induction chemotherapy irrespective of the FLT3-ITD mutation status. These findings provide insight into the pathophysiology and help to understand the favorable clinical outcome of patients with NPM1(+) AML.
Schneider
Friederike
F
Department of Medicine III, University Hospital Munich, Germany.
Hoster
Eva
E
Unterhalt
Michael
M
Schneider
Stephanie
S
Dufour
Annika
A
Benthaus
Tobias
T
Mellert
Gudrun
G
Zellmeier
Evelin
E
Bohlander
Stefan K
SK
Feuring-Buske
Michaela
M
Buske
Christian
C
Braess
Jan
J
Fritsch
Susanne
S
Heinecke
Achim
A
Sauerland
Maria C
MC
Berdel
Wolfgang E
WE
Buechner
Thomas
T
Woermann
Bernhard J
BJ
Hiddemann
Wolfgang
W
Spiekermann
Karsten
K
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001752:Blast Crisis / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D055029:Inverted Repeat Sequences; D007621:Karyotyping; D007694:Killer Cells, Natural; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D012074:Remission Induction; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3