DIFFERENTIATION INHIBITORY FACTOR NM23 AS A NEW PROGNOSTIC FACTOR IN ACUTE MONOCYTIC LEUKEMIA

Differentiation inhibitory factor (nm23 protein) inhibited the inducti on of differentiation of mouse myeloid leukemia M1 and WEHI-3BD(+) and human erythroleukemia HEL, KU812, and K562 cells. Block of differenti ation may be associated with the aggressive behavior of leukemia. To e xamine the role of nm23 in human myeloid leukemia, we investigated the relative levels of nm23-H1, nm23-H2, and c-myc transcripts in 42 pati ents with acute myelogenous leukemia (AML), and in 5 with chronic myel ogenous leukemia at chronic phase by reverse transcriptase polymerase chain reaction, The expression of nm23-H1 and -H2 but not of c-myc in AML was significantly higher than that in normal blood cells. Among AM Ls, acute monocytic leukemia (presentation with AML-M5 morphology) was especially associated with elevated nm23-H1 and -H2 mRNA levels, On t he other hand, the elevated levels of c-myc expression in AML-M5 were less evident, An analysis of correlation between nm23 expression and c linicopathological parameters showed that resistance to initial chemot herapy is associated with increased nm23-H1 mRNA levels and that a hig h initial white blood cell count is associated with increased nm23-H2 mRNA levels. Elevated nm23-H1 mRNA levels were associated with signifi cantly reduced the overall survival of AML, especially of AML-M5 patie nts. The present results indicate that nm23-H1 and -H2 are overexpress ed in AML and especially nm23-H1 gene expression predicts the prognosi s of AML especially of AML-M5. (C) 1996 by The American Society of Hem atology.