title: Prognostic significance of combined MN1, ERG, BAALC, and EVI1 (MEBE) expression in patients with myelodysplastic syndromes.
abstract: Overexpression of MN1, ERG, BAALC, and EVI1 (MEBE) genes in cytogenetically normal acute myeloid leukemia (AML) patients is associated with poor prognosis, but their prognostic effect in patients with myelodysplastic syndromes (MDS) has not been studied systematically. Expression data of the four genes from 140 MDS patients were combined in an additive score, which was validated in an independent patient cohort of 110 MDS patients. A high MEBE score, defined as high expression of at least two of the four genes, predicted a significantly shorter overall survival (OS) (HR 2.29, 95 % CI 1.3-4.09, P= .005) and time to AML progression (HR 4.83, 95 % CI 2.01-11.57, P< .001) compared to a low MEBE score in multivariate analysis independent of karyotype, percentage of bone marrow blasts, transfusion dependence, ASXL1, and IDH1 mutation status. In a validation cohort of 110 MDS patients, a high MEBE score predicted shorter OS (HR 1.77; 95 % CI 1.04-3.0, P= .034) and time to AML progression (HR 3.0, 95 % CI 1.17-7.65, P= .022). A high MEBE expression score is an unfavorable prognostic marker in MDS and is associated with an increased risk for progression to AML. Expression of the MEBE genes is regulated by FLI1 and c-MYC, which are potential upstream targets of the MEBE signature.
authors.affiliation: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Thol
authors.forename: Haiyang
authors.initials: H
authors.lastname: Yun
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Sonntag
authors.forename: Frederik
authors.initials: F
authors.lastname: Damm
authors.forename: Eva M
authors.initials: EM
authors.lastname: Weissinger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Katharina
authors.initials: K
authors.lastname: Wagner
authors.forename: Michael
authors.initials: M
authors.lastname: Morgan
authors.forename: Martin
authors.initials: M
authors.lastname: Wichmann
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.forename: Gesine
authors.initials: G
authors.lastname: Bug
authors.forename: Oliver
authors.initials: O
authors.lastname: Ottmann
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: David
authors.initials: D
authors.lastname: Bowen
authors.forename: Ken
authors.initials: K
authors.lastname: Mills
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011237:Predictive Value of Tests; D011289:Preleukemia / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D011519:Proto-Oncogenes / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000071230:Transcriptional Regulator ERG; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D054928:Validation Studies as Topic
chemical_list: C442828:BAALC protein, human; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C506524:MN1 protein, human; D009363:Neoplasm Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D025521:Tumor Suppressor Proteins