Plasma levels of the differentiation inhibitory factor nm23-H1 protein and their clinical implications in acute myelogenous leukemia.

Abstract

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.

• Authors: N Niitsu, J Okabe-Kado, M Nakayama, N Wakimoto, A Sakashita, N Maseki, K Motoyoshi, M Umeda, Y Honma
• Journal: Blood (Blood) Vol. 96 Issue 3 Pg. 1080-6 (Aug 01 2000) ISSN: 0006-4971 [Print] United States
• PMID: 10910925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• NM23 Nucleoside Diphosphate Kinases
• Transcription Factors
• NME1 protein, human
• Nucleoside-Diphosphate Kinase
• Monomeric GTP-Binding Proteins

Topics

• Adult
• Aged
• Antigens, Neoplasm (blood)
• Biomarkers, Tumor
• Female
• Humans
• Leukemia, Myeloid, Acute (blood, physiopathology)
• Male
• Middle Aged
• Monomeric GTP-Binding Proteins (blood)
• Multivariate Analysis
• NM23 Nucleoside Diphosphate Kinases
• Nucleoside-Diphosphate Kinase
• Prognosis
• Transcription Factors (blood)