title: ID1 expression associates with other molecular markers and is not an independent prognostic factor in cytogenetically normal acute myeloid leukaemia.
abstract: In acute myeloid leukaemia with normal karyotype (CN-AML), gene mutations (e.g. NPM1, FLT3, CEBPA) as well as deregulated gene expression affect outcome. High expression of ID1 was described as a negative prognostic factor. We have shown that CEBPA regulates ID1 expression. Therefore, we analysed the prognostic impact of ID1 expression in 269 patients (aged 16-60 years) with CN-AML in the context of other molecular markers, particularly CEBPA mutations. ID1(high) status was an independent negative prognostic factor for overall survival (OS) in multivariate analysis when analysed together with age, extramedullary disease, platelets, expression of BAALC and WT1, FLT3-internal tandem duplication, NPM1, WT1 single nucleotide polymorphism rs16754 and IDH1. ID1 expression was higher in CEBPA wildtype patients than in patients with monoallelic CEBPA mutations and these patients showed higher ID1 expression compared to patients with biallelic CEBPA mutations. Thus, when CEBPA mutations were considered, ID1 expression lost its prognostic impact. Likewise, the negative impact of ID1(high) status on relapse-free survival (RFS) was lost when CEBPA mutations were included in the analysis. In CEBPA wildtype patients, ID1 expression had no impact on complete remission-rate, OS or RFS. In conclusion, CEBPA mutations seem to deregulate ID1 expression. Therefore, ID1 expression is not an independent prognostic factor in CN-AML.
authors.affiliation: Department of Haematology, Haemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Damm
authors.affiliation: Department of Haematology, Haemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wagner
authors.affiliation: Department of Haematology, Haemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Görlich
authors.affiliation: Department of Haematology, Haemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Department of Haematology, Haemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Thol
authors.affiliation: Department of Haematology, Haemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Yun
authors.affiliation: Department of Haematology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Ruud
authors.initials: R
authors.lastname: Delwel
authors.affiliation: Department of Haematology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Peter J M
authors.initials: PJM
authors.lastname: Valk
authors.affiliation: Department of Haematology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.affiliation: Department of Haematology, Haemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: Department of Haematology, Haemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D000090243:Nucleophosmin; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012074:Remission Induction; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000090243:Nucleophosmin