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

A previous study reported that a nondifferentiating myeloid leukemia cell l ine produced differentiation-inhibiting factors. One of the factors was pur ified as a homologue of the nm23 genes. The nm23 genes were overexpressed i n acute myelogenous leukemia (AML) cells, and a higher level of nm23 gene e xpression was correlated with a poor prognosis in AML, The present study de termined the plasma levels of nm23-H1 protein by enzyme-linked immunosorben t assay and assessed the association between this level and the clinical ou tcome in 102 patients with AML, The plasma concentration of nm23-H1 was hig her in patients with AML than in normal controls (P = .0001). Plasma nm23-H 1 levels were correlated with the product of the intracellular nm23 messeng er RNA (mRNA) level and the white blood cell count, but not with the mRNA l evel alone, Therefore, nm23-H1 plasma levels probably depend on the total m ass of leukemic cells overexpressing the nm23-H1 gene. Overall survival was lower in patients with higher plasma nm23-H1 levels than in those with low er levels. Multivariate analysis using the Cox proportional hazard model sh owed that elevated plasma nm23-H1 levels significantly contributed to the p rognosis of AML patients. Furthermore, the plasma nm23-H1 levels were inves tigated in 70 patients with other hematologic neoplasms, including 6 with a cute lymphoblastic leukemia, 13 with chronic myelogenous leukemia, and 12 w ith myelodysplastic syndrome. Plasma nm23-H1 levels were significantly high er in all of these hematologic neoplasms than in normal controls. Increased plasma levels of nm23-H1 may have prognostic value in these hematologic ma lignancies as well as in AML. (C) 2000 by The American Society of Hematolog y.