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.
Publication types
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Clinical Trial
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Animals
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Biomarkers, Tumor / biosynthesis*
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Biomarkers, Tumor / genetics
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Cytogenetic Analysis / methods
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Disease-Free Survival
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Female
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Gene Expression Regulation, Leukemic*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Humans
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Leukemia, Lymphocytic, Chronic, B-Cell / genetics
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Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
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Leukemia, Lymphocytic, Chronic, B-Cell / mortality
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Leukemia, Lymphocytic, Chronic, B-Cell / therapy
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy
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Leukemia, Myeloid, Acute / genetics
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Leukemia, Myeloid, Acute / metabolism*
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Leukemia, Myeloid, Acute / mortality
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Leukemia, Myeloid, Acute / therapy
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Male
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Mice
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Middle Aged
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Nucleophosmin
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Oncogene Proteins, Fusion / biosynthesis
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Oncogene Proteins, Fusion / genetics
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Predictive Value of Tests
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Reverse Transcriptase Polymerase Chain Reaction
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Survival Rate
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Trans-Activators
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
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Tumor Suppressor Proteins / biosynthesis*
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Tumor Suppressor Proteins / genetics
Substances
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Biomarkers, Tumor
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Homeodomain Proteins
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MN1 protein, human
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MN1-TEL fusion protein, human
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NPM1 protein, human
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Npm1 protein, mouse
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Oncogene Proteins, Fusion
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Trans-Activators
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Transcription Factors
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Tumor Suppressor Proteins
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homeobox protein HOXA9
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Nucleophosmin