Plasma levels of the differentiation inhibitory factor nm23-H1 protein and their clinical implications in acute myelogenous leukemia.
A previous study reported that a nondifferentiating myeloid leukemia cell line produced differentiation-inhibiting factors. One of the factors was purified as a homologue of the nm23 genes. The nm23 genes were overexpressed in acute myelogenous leukemia (AML) cells, and a higher level of nm23 gene expression was correlated with a poor prognosis in AML. The present study determined the plasma levels of nm23-H1 protein by enzyme-linked immunosorbent assay and assessed the association between this level and the clinical outcome in 102 patients with AML. The plasma concentration of nm23-H1 was higher in patients with AML than in normal controls (P =.0001). Plasma nm23-H1 levels were correlated with the product of the intracellular nm23 messenger RNA (mRNA) level and the white blood cell count, but not with the mRNA level alone. Therefore, nm23-H1 plasma levels probably depend on the total mass of leukemic cells overexpressing the nm23-H1 gene. Overall survival was lower in patients with higher plasma nm23-H1 levels than in those with lower levels. Multivariate analysis using the Cox proportional hazard model showed that elevated plasma nm23-H1 levels significantly contributed to the prognosis of AML patients. Furthermore, the plasma nm23-H1 levels were investigated in 70 patients with other hematologic neoplasms, including 6 with acute lymphoblastic leukemia, 13 with chronic myelogenous leukemia, and 12 with myelodysplastic syndrome. Plasma nm23-H1 levels were significantly higher in all of these hematologic neoplasms than in normal controls. Increased plasma levels of nm23-H1 may have prognostic value in these hematologic malignancies as well as in AML.
First Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
N
N
Niitsu
J
J
Okabe-Kado
M
M
Nakayama
N
N
Wakimoto
A
A
Sakashita
N
N
Maseki
K
K
Motoyoshi
M
M
Umeda
Y
Y
Honma
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000097:blood*; D015999:Multivariate Analysis; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D011379:Prognosis; D014157:Transcription Factors / Q000097:blood*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins