title: RT-PCR and FISH analysis of acute myeloid leukemia with t(8;16)(p11;p13) and chimeric MOZ and CBP transcripts: breakpoint cluster region and clinical implications.
abstract: The translocation t(8;16)(p11;p13) is associated with acute myeloid leukemia displaying monocytic differentiation (AML FAB M4/5) and fuses the MOZ (also named MYST3) gene (8p11) with the CBP (also named CREBBP) gene (16p13). Detection of the chimeric RNA fusions has proven difficult; only three studies have described successful amplification of the chimeric MOZ-CBP and CBP-MOZ fusions by reverse transcriptase-polymerase chain reaction (RT-PCR). We analyzed four cases of AML M4/5 with t(8;16)(p11;p13) by RT-PCR and fluorescence in situ hybridization (FISH) and characterized the reciprocal RNA fusions from three cases. We cloned both genomic translocation breakpoints from one case by long-range PCR and successfully applied RT-PCR to monitor minimal residual disease (MRD) between clinical complete remission and relapse. In three cases, the genomic breakpoints occurred in MOZ intron 16 and CBP intron 2. In one case, no fusion transcript was detected. The available data suggest clustering of t(8;16)(p11;p13) breakpoints in these introns leading to reciprocal in-frame MOZ exon 16/CBP exon 3 and in-frame CBP exon 2/MOZ exon 17 chimeric transcripts in the majority of cases. The described RT-PCR strategy may be valuable both for the routine detection of the t(8;16)(p11;p13) as well as for monitoring of MRD in this prognostically unfavorable patient group.
authors.affiliation: Department of Internal Medicine, Division of Hematology, University Medical Center, Graz, Austria. helmut.schmidt@klinikum-graz.at
authors.forename: H H
authors.initials: HH
authors.lastname: Schmidt
authors.forename: S
authors.initials: S
authors.lastname: Strehl
authors.forename: D
authors.initials: D
authors.lastname: Thaler
authors.forename: D
authors.initials: D
authors.lastname: Strunk
authors.forename: H
authors.initials: H
authors.lastname: Sill
authors.forename: W
authors.initials: W
authors.lastname: Linkesch
authors.forename: U
authors.initials: U
authors.lastname: Jäger
authors.forename: W
authors.initials: W
authors.lastname: Sperr
authors.forename: H T
authors.initials: HT
authors.lastname: Greinix
authors.forename: M
authors.initials: M
authors.lastname: König
authors.forename: W
authors.initials: W
authors.lastname: Emberger
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D050882:CREB-Binding Protein; D002454:Cell Differentiation; D002678:Chimera; D002885:Chromosomes, Human, Pair 16; D002898:Chromosomes, Human, Pair 8; D005260:Female; D051548:Histone Acetyltransferases; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D018365:Neoplasm, Residual / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D009687:Nuclear Proteins; D015534:Trans-Activators; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human