title: Rare CBFB-MYH11 fusion transcripts in AML with inv(16)/t(16;16) are associated with therapy-related AML M4eo, atypical cytomorphology, atypical immunophenotype, atypical additional chromosomal rearrangements and low white blood cell count: a study on 162 patients.
abstract: The spectrum of CBFB-MYH11 fusion transcripts in acute myeloid leukemia (AML) M4eo with inv(16)/t(16;16) is heterogeneous. Approximately 85% show type A CBFB-MYH11 fusion transcripts. In addition, more than 10 different fusion transcripts have been reported. The prognostic impact and biological background of rare fusion transcripts remain open. In this study, a molecular characterization of CBFB-MYH11 transcripts in 162 patients with CBFB-MYH11 positive AML at diagnosis was performed. In total, 128 patients (79.0%) showed the fusion transcript type A, whereas nine different rare CBFB-MYH11 fusion genes were detected in 34 cases (21.0%). Rare fusion transcripts were found more frequently in therapy-related AML (P=0.0106). Numerical gains of the chromosomes 8, 21 and 22 were more frequently associated with type A (28.3%) than with rare fusions (12.9%) (P=0.012). Median white blood cell (WBC) count was higher in type A (35.4 G/l; range=1.1-279 G/l) than in cases with rare types (7.8 G/l; range=0.8-148.0 G/l) (P<0.0001). Rare fusion transcripts were correlated with an atypical cytomorphology not primarily suggestive for the FAB subtype M4eo (P=0.0203). Immunophenotype revealed lower CD2, CD13, CD33 and CD90 levels than in type A fusion cases (P=0.036, 0.002, 0.029 and 0.045, respectively). However, the type of fusion was not an independent prognostic parameter.
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany. susanne.schnittger@mll-online.com
authors.forename: S
authors.initials: S
authors.lastname: Schnittger
authors.forename: U
authors.initials: U
authors.lastname: Bacher
authors.forename: C
authors.initials: C
authors.lastname: Haferlach
authors.forename: W
authors.initials: W
authors.lastname: Kern
authors.forename: T
authors.initials: T
authors.lastname: Haferlach
mesh_terms: D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16; D015331:Cohort Studies; D050658:Core Binding Factor beta Subunit / Q000235:genetics*; D005260:Female; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018995:Myosin Heavy Chains / Q000235:genetics*; D016019:Survival Analysis; D014158:Transcription, Genetic; D014178:Translocation, Genetic
chemical_list: C493692:CBFB protein, human; D050658:Core Binding Factor beta Subunit; C509903:MYH11 protein, human; D018995:Myosin Heavy Chains