The prognostic impact of 17p (p53) deletion in 2272 adults with acute myeloid leukemia.
Loss of p53 -- a tumor suppressor gene located on the short arm of chromosome 17 (band 17p13.1) -- was detected in 105 out of 2272 (5%) adult acute myeloid leukemia (AML) patients who took part in the Study Alliance Leukemia AML96 and AML2003 multi center trials. There were 85 patients with 17p (p53) deletion with multiple aberrations and 20 patients with a 17p (p53) deletion as single aberration or with only one additional chromosomal abnormality. None of the p53-deleted patients displayed additional low-risk aberrations, like t(8;21) or inv(16). Significant positive association between p53 deletion and other high-risk factors was identified for del(5q) (P<0.001), -5 (P<0.001) and -7 (P<0.05). The molecular risk factors FLT3-ITD and NPM1 mutation showed an inverse correlation to the p53 deletion in complex aberrant patients (P<0.001). The multivariate analysis revealed p53 deletion without multiple aberrations as an independent negative prognostic factor for disease-free survival (P<0.001), relapse risk (P=0.028) and overall survival (P<0.001). Thus, the single p53 deletion should be considered as a high-risk aberration for future risk-adapted treatment strategies in AML.
Seifert
H
H
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Dresden, Germany.
Mohr
B
B
Thiede
C
C
Oelschlägel
U
U
Schäkel
U
U
Illmer
T
T
Soucek
S
S
Ehninger
G
G
Schaich
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002886:Chromosomes, Human, Pair 17; D018572:Disease-Free Survival; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3