Prognostic significance of the cell cycle inhibitor p27Kip1 in acute myeloid leukemia.
There are few molecular biologic determinants that are prognostic for patients with acute myeloid leukemia (AML). Hence, we examined whether cellular levels of the cyclin-dependent kinase inhibitor p27Kip1 in acute myeloid leukemia could be used to predict clinical outcome in AML. Using immunoblot analysis, levels of p27 were assessed in blast cells from 72 AML patients who were registered and treated by the identical chemotherapy protocol. AML cases were classified into three groups on the basis of the percentage of the expression level of p27 compared to a control cell line. AML cases exhibiting p27 expression at low, moderate, and high levels were 43, 9, and 20 cases, respectively. No significant differences in the rates of complete remission (CR) were observed among the three groups. Although the level of p27 expression was not correlated with any other possible prognostic markers, such as age, white blood cell count, chromosome abnormalities, and FAB subclasses, patients with high p27 expression had a significantly increased disease-free survival (DFS) (78% vs 19%, P = 0.004). We further examined the expression of cyclin E at the protein level in all 72 AML cases. We observed a statistically significant correlation between a high cyclin E level and a high p27 level (P < 0.005). However, we failed to find any correlation between the rates of CR or DFS and cyclin E expression. The present study reveals that levels of p27 expression can be one of the useful prognostic molecular markers for AML. Leukemia (2000) 14, 28-33.
Yokozawa
T
T
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Towatari
M
M
Iida
H
H
Takeyama
K
K
Tanimoto
M
M
Kiyoi
H
H
Motoji
T
T
Asou
N
N
Saito
K
K
Takeuchi
M
M
Kobayashi
Y
Y
Miyawaki
S
S
Kodera
Y
Y
Ohno
R
R
Saito
H
H
Naoe
T
T
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019927:Cyclin E / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D011379:Prognosis; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019927:Cyclin E; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases