High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics

被引:186
作者
Heuser, Michael
Beutel, Gernot
Krauter, Juergen
Doehner, Konstanze
von Neuhoff, Nils
Schlegelberger, Brigitte
Ganser, Arnold
机构
[1] Hannover Med Sch, Dept Hematol Hemostasis & Oncol, D-3000 Hannover, Germany
[2] Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany
[3] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany
关键词
D O I
10.1182/blood-2006-04-014845
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (HPCs) and, in cooperation with HOXA9, induce AML. We quantified MN1 expression by real-time reverse transcriptase-polymerase chain reaction (RTPCR) in 142 adult patients with AML 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 survivals (P = .03). In multivariate analysis, MN1 expression was an independent prognostic marker (P = .02) in addition to age and Eastern Cooperative Oncology Group (ECOG) performance status. Excluding patients with NPM1(mutated)/FLT3ITD(negative), 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 HPCs compared with differentiated cells and was down-regulated during in vitro differentiation of CD34(+) cells, suggesting a functional role in HPCs. In conclusion, our data suggest MN1 overexpression as a new prognostic marker in AML with normal cytogenetics.
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页码:3898 / 3905
页数:8
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