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Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 1080-1086
Plasma levels of the differentiation inhibitory factor nm23-H1
protein and their clinical implications in acute myelogenous
leukemia
Nozomi Niitsu,
Junko Okabe-Kado,
Michihiro Nakayama,
Naoki Wakimoto,
Akiko Sakashita,
Nobuo Maseki,
Kazuo Motoyoshi,
Masanori Umeda, and
Yoshio Honma
From the First Department of Internal Medicine, Toho University
School of Medicine, Tokyo; Research Institute and Hospital, Saitama
Cancer Center, Saitama; and the Third Department of Internal Medicine,
National Defense Medical College, Saitama, Japan.
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.
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