High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics
- 1 December 2006
- journal article
- clinical trial
- Published by American Society of Hematology in Blood
- Vol. 108 (12), 3898-3905
- https://doi.org/10.1182/blood-2006-04-014845
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 NPM1mutated/FLT3ITDnegative, 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.Keywords
This publication has 42 references indexed in Scilit:
- Conditional MN1-TEL knock-in mice develop acute myeloid leukemia in conjunction with overexpression of HOXA9Blood, 2005
- MN1-TEL myeloid oncoprotein expressed in multipotent progenitors perturbs both myeloid and lymphoid growth and causes T-lymphoid tumors in miceBlood, 2005
- Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutationsBlood, 2005
- The 1,25(OH)2D3-Regulated Transcription Factor MN1 Stimulates Vitamin D Receptor-Mediated Transcription and Inhibits Osteoblastic Cell ProliferationMolecular Endocrinology, 2005
- Targeted Disruption of the Mn1 Oncogene Results in Severe Defects in Development of Membranous Bones of the Cranial SkeletonMolecular and Cellular Biology, 2005
- The MN1 oncoprotein synergizes with coactivators RAC3 and p300 in RAR-RXR-mediated transcriptionOncogene, 2003
- Integration of amplified BCR/ABL fusion genes into the short arm of chromosome 17 as a novel mechanism of disease progression in chronic myeloid leukemiaGenes, Chromosomes and Cancer, 2001
- The MN1-TEL Fusion Protein, Encoded by the Translocation (12;22)(p13;q11) in Myeloid Leukemia, Is a Transcription Factor with Transforming ActivityMolecular and Cellular Biology, 2000
- Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression MonitoringScience, 1999
- Proposed Revised Criteria for the Classification of Acute Myeloid LeukemiaAnnals of Internal Medicine, 1985