Low SMC1A protein expression predicts poor survival in acute myeloid leukemia.
Age is a strong adverse prognostic factor in acute myeloid leukemia. Little is known about the biology of acute myeloid leukemia in elderly patients. The aim of this study was to identify genes with age-dependent changes of expression in leukemic blasts and their relevance for the patient prognosis. Gene expression profiling was carried out by mRNA microarray analysis from blasts of 67 adult acute myeloid leukemia patients of different age (range, 17-80 years). Among the genes that correlated with age, PRPF4 and SMC1A were selected for protein expression studies on a tissue array containing bone marrow histologies of 135 patients with newly diagnosed AML of different ages. A significant correlation between mRNA expression levels and patient age was shown by 131 genes. Increasing age was associated with significantly decreased mRNA levels of SMC1A. On the protein level, expression of SMC1A was low or absent in 74 out of 116 acute myeloid leukemia specimens. Importantly, patients with low protein expression levels of SMC1A experienced significantly shortened event free (2.6 months versus 10.3 months, p=0.003) and overall survival (10.4 months versus 22.6 months, p=0.015). The SMC1A protein expression level remained a significant prognostic factor for event free survival (p=0.014) with a borderline significance for overall survival (p=0.066) in a multivariate analysis. SMC1A protein expression might play a role in the determination of the prognosis and might have possible implications in therapy decision in patients with acute myeloid leukemia.
Department of Medicine A, University Hospital of Münster, D-48149 Münster, Germany.
Claudia
C
Hömme
Utz
U
Krug
Nicola
N
Tidow
Bernd
B
Schulte
Gabriele
G
Kühler
Hubert
H
Serve
Horst
H
Bürger
Wolfgang E
WE
Berdel
Martin
M
Dugas
Achim
A
Heinecke
Thomas
T
Büchner
Steffen
S
Koschmieder
Carsten
C
Müller-Tidow
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult; D000098550:Structural Maintenance of Chromosome Protein 1
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009363:Neoplasm Proteins; D000098550:Structural Maintenance of Chromosome Protein 1