title: Gene expression of BAALC, CDKN1B, ERG, and MN1 adds independent prognostic information to cytogenetics and molecular mutations in adult acute myeloid leukemia.
abstract: Expression of BAALC, ERG, and MN1 is associated with outcome in normal karyotype acute myeloid leukemia (AML). In this study, the expression of these markers and of EVI1 and CDKN1B was determined using oligonucleotide microarrays in 286 AML comprising all cytogenetic groups. Higher expression of each gene was associated with an inferior outcome: CDKN1B, median overall survival (mOS): 14.9 months vs. not reached (nr), P = 0.005, median event-free survival (mEFS): 9.7 vs. 31.0 months, P = 0.013; BAALC, no impact on OS, mEFS: 6.2 vs. 13.0 months, P = 0.03; ERG: mOS: 12.5 months vs. nr, P = 0.002, mEFS: 8.1 vs. 15.7 months, P = 0.001; MN1: mOS: 12.3 months vs. nr, P = 0.004, mEFS: 8.1 vs. 16.7 months, P = 0.001. A multivariate analysis revealed an independent impact on OS for CDKN1B, ERG, and MN1 expression. A novel score based on BAALC, CDKN1B, ERG, and MN1 expression had an impact on OS and EFS independent of cytogenetics and age. A score taking into account gene expression and karyotype allowed the separation of four prognostic groups with significant differences in OS and EFS (OS at 2 years: 90.4%, 56.4%, 34.0%, 12.6%; mEFS: n.r., 18.1 months, 8.7 months, 2.5 months). The impact on outcome of this score was independent of NPM1mut/FLT3-ITD- status, MLL-PTD, and age.
authors.affiliation: MLL - Munich Leukemia Laboratory, Munich, Germany. claudia.haferlach@mll.com
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Sonja
authors.initials: S
authors.lastname: Schindela
authors.forename: Alexander
authors.initials: A
authors.lastname: Kohlmann
authors.forename: Tamara
authors.initials: T
authors.lastname: Alpermann
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D018572:Disease-Free Survival; D015870:Gene Expression; D020869:Gene Expression Profiling; D005858:Germany; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015534:Trans-Activators / Q000235:genetics; D000071230:Transcriptional Regulator ERG; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C442828:BAALC protein, human; D014408:Biomarkers, Tumor; C436291:CDKN1B protein, human; C072312:ERG protein, human; C506524:MN1 protein, human; D009363:Neoplasm Proteins; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27