Serum nm23-H1 protein as a prognostic factor in hematological malignancies.

ABSTRACT

A nondifferentiating mouse myeloid leukemia cell line produces differentiation-inhibiting factors. One of these factors was purified as a homologue of nm23. The nm23 gene was isolated as a metastasis-suppressor gene that exhibits low expression in high-level metastatic cancer cells. The nm23 gene was overexpressed in acute myelogenous leukemia (AML) cells and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML. Multivariate analysis of putative prognostic factors revealed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. The overexpression of nm23-H1 was also observed in various hematological neoplasms. To use nm23 overexpression to determine the prognosis for lymphoma, we established an enzyme-linked immunosorbent assay (ELISA) technique to determine the serum level of nm23-H1 protein. This assay is far simpler than that used to determine nm23 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Using this system, we measured nm23-H1 protein levels in many hematological malignancies. Serum nm23-HI levels were significantly higher in patients with all of the hematological neoplasms tested (AML, chronic myelogenous leukemia, acute lymphoblastic leukemia, (ALL) myelodysplastic syndrome (MDS) and malignant lymphomas) than in normal controls. An elevated serum nm23-H1 protein concentration predicted a poor outcome for AML and non-Hodgkin's lymphoma. Especially in diffuse large B-cell lymphoma (DLBCL), seram nm23-H1 protein levels were an important prognostic factor in planning an appropriate treatment strategy for DLBCL. The serum nm23-H I protein levels probably depend on the total mass of malignant cells overexpressing nm23-H1.