Submitted April 4, 2006
Accepted July 18, 2006
High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics
Michael Heuser*, Gernot Beutel, Juergen Krauter, Konstanze Dohner, Nils von Neuhoff, Brigitte Schlegelberger, and Arnold Ganser
Hannover Medical School, Hannover, Germany
University Hospital of Ulm, Ulm, Germany
* Corresponding author; email: mheuser{at}bccrc.ca.
The translocation t(12;22) involves MN1 and TEL and is rarely found in acute myeloid leukemia (AML). Recently, it has been shown in a mouse model that the fusion protein MN1-TEL can promote growth of primitive hematopoietic progenitor cells (HPC) and, in cooperation with HOXA9, induce AML. We quantified MN1 expression by real-time RT-PCR in 142 adult AML patients with normal cytogenetics treated uniformly in trial AML-SHG 01/99. AML samples were dichotomized at the median MN1 expression. High MN1 expression was significantly correlated with unmutated NPM1 (P<.001), poor response to the first course of induction treatment (P=.02), a higher relapse rate (P=.03), and shorter relapse-free (P=.002) and overall survival (P=.03). In multivariate analysis, MN1 expression was an independent prognostic marker (P=.02) in addition to age and ECOG performance status. Excluding NPM1mutated/FLT3ITDnegative patients, high MN1 expression was associated with shorter relapse-free survival (P=.057). MN1 was highly expressed in some patients with acute lymphoblastic, but not chronic lymphocytic or myeloid leukemia. MN1 was highly expressed in HPC compared to differentiated cells, and was downregulated during in-vitro differentiation of CD34+ cells, suggesting a functional role in HPC. In conclusion, our data suggest MN1 overexpression as a new prognostic marker in AML with normal cytogenetics.
