PMID- 16051734
OWN - NLM
STAT- MEDLINE
DCOM- 20060118
LR  - 20220408
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 106
IP  - 12
DP  - 2005 Dec 1
TI  - Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with 
      acute myeloid leukemia and normal cytogenetics: interaction with other gene 
      mutations.
PG  - 3740-6
AB  - To assess the prognostic relevance of mutations in the NPM1 gene encoding a 
      nucleocytoplasmic shuttle protein in younger adults with acute myeloid leukemia 
      (AML) and normal cytogenetics, sequencing of NPM1 exon 12 was performed in 
      diagnostic samples from 300 patients entered into 2 consecutive multicenter 
      trials of the AML Study Group (AMLSG). Treatment included intensive 
      double-induction therapy and consolidation therapy with high cumulative doses of 
      high-dose cytarabine. NPM1 mutations were identified in 48% of the patients 
      including 12 novel sequence variants, all leading to a frameshift in the 
      C-terminus of the nucleophosmin 1 (NPM1) protein. Mutant NPM1 was associated with 
      specific clinical, phenotypical, and genetic features. Statistical analysis 
      revealed a significant interaction of NPM1 and FLT3 internal tandem duplications 
      (ITDs). NPM1 mutations predicted for better response to induction therapy and for 
      favorable overall survival (OS) only in the absence of FLT3 ITD. Multivariable 
      analysis for OS revealed combined NPM1-mutated/FLT3 ITD-negative status, CEBPA 
      mutation status, availability of a human leukocyte antigen (HLA)-compatible 
      donor, secondary AML, and lactate dehydrogenase (LDH) as prognostic factors. In 
      conclusion, NPM1 mutations in the absence of FLT3 ITD define a distinct molecular 
      and prognostic subclass of young-adult AML patients with normal cytogenetics.
FAU - Dohner, Konstanze
AU  - Dohner K
AD  - Department of Internal Medicine III, University Hospital of Ulm, Robert-Koch-Str 
      8, 89081 Ulm, Germany. konstanze.doehner@medizin.uni-ulm.de
FAU - Schlenk, Richard F
AU  - Schlenk RF
FAU - Habdank, Marianne
AU  - Habdank M
FAU - Scholl, Claudia
AU  - Scholl C
FAU - Rucker, Frank G
AU  - Rucker FG
FAU - Corbacioglu, Andrea
AU  - Corbacioglu A
FAU - Bullinger, Lars
AU  - Bullinger L
FAU - Frohling, Stefan
AU  - Frohling S
FAU - Dohner, Hartmut
AU  - Dohner H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050728
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CCAAT-Binding Factor)
RN  - 0 (NPM1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 117896-08-9 (Nucleophosmin)
RN  - EC 2.7.10.1 (FLT3 protein, human)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
SB  - IM
MH  - Acute Disease
MH  - Adolescent
MH  - Adult
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - CCAAT-Binding Factor/genetics
MH  - Clinical Trials as Topic
MH  - Female
MH  - Humans
MH  - Leukemia, Myeloid/*genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Nuclear Proteins/*genetics
MH  - Nucleophosmin
MH  - Polymerase Chain Reaction
MH  - Prognosis
MH  - Survival Analysis
MH  - fms-Like Tyrosine Kinase 3/genetics
EDAT- 2005/07/30 09:00
MHDA- 2006/01/19 09:00
CRDT- 2005/07/30 09:00
PHST- 2005/07/30 09:00 [pubmed]
PHST- 2006/01/19 09:00 [medline]
PHST- 2005/07/30 09:00 [entrez]
AID - S0006-4971(20)66905-1 [pii]
AID - 10.1182/blood-2005-05-2164 [doi]
PST - ppublish
SO  - Blood. 2005 Dec 1;106(12):3740-6. doi: 10.1182/blood-2005-05-2164. Epub 2005 Jul 
      28.