title: High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics.
abstract: 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 (RT-PCR) 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.
authors.affiliation: British Columbia Cancer Research Centre, 675 West 10th Ave, Vancouver, BC, Canada. heuser.michael@mh-hannover.de
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
authors.forename: Gernot
authors.initials: G
authors.lastname: Beutel
authors.forename: Juergen
authors.initials: J
authors.lastname: Krauter
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.forename: Nils
authors.initials: N
authors.lastname: von Neuhoff
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D020732:Cytogenetic Analysis / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D008297:Male; D051379:Mice; D008875:Middle Aged; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C506524:MN1 protein, human; C417770:MN1-TEL fusion protein, human; C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C097899:homeobox protein HOXA9; D000090243:Nucleophosmin