Original Article

Annals of Hematology

, Volume 91, Issue 8, pp 1221-1233

First online:

Prognostic significance of combined MN1, ERG, BAALC, and EVI1 (MEBE) expression in patients with myelodysplastic syndromes

  • Felicitas TholAffiliated withDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School
  • , Haiyang YunAffiliated withDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School
  • , Ann-Kathrin SonntagAffiliated withDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School
  • , Frederik DammAffiliated withDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School
  • , Eva M. WeissingerAffiliated withDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School
  • , Jürgen KrauterAffiliated withDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School
  • , Katharina WagnerAffiliated withDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School
  • , Michael MorganAffiliated withDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School
  • , Martin WichmannAffiliated withDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School
    • , Gudrun GöhringAffiliated withInstitute of Cell and Molecular Pathology, Hannover Medical School
    • , Gesine BugAffiliated withDepartment of Internal Medicine III, University of Frankfurt
    • , Oliver OttmannAffiliated withDepartment of Internal Medicine III, University of Frankfurt
    • , Wolf-Karsten HofmannAffiliated withDepartment of Hematology and Oncology, University Hospital Mannheim
    • , Axel SchambachAffiliated withDepartment of Experimental Hematology, Hannover Medical School
    • , Brigitte SchlegelbergerAffiliated withInstitute of Cell and Molecular Pathology, Hannover Medical School
    • , Torsten HaferlachAffiliated withMLL, Munich Leukemia Laboratory
    • , David BowenAffiliated withSt James’s Institute of Oncology, Leeds Teaching Hospitals
    • , Ken MillsAffiliated withCentre for Cancer Research and Cell Biology, Queen’s University Belfast
    • , Arnold GanserAffiliated withDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School
    • , Michael HeuserAffiliated withDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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.

Keywords

MDS Prognosis Gene expression Score Splicing