title: Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16) in a prospective series of adults with de novo acute myeloid leukemia: a Cancer and Leukemia Group B Study.
abstract: OBJECTIVE
  To prospectively compare cytogenetics and reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of t(8;21)(q22;q22) and inv(16)(p13q22)/t(16;16)(p13;q22), aberrations characteristic of core-binding factor (CBF) acute myeloid leukemia (AML), in 284 adults newly diagnosed with primary AML.
  
  
  METHODS
  Cytogenetic analyses were performed at local laboratories, with results reviewed centrally. RT-PCR for AML1/ETO and CBFbeta/MYH11 was performed centrally.
  
  
  RESULTS
  CBF AML was ultimately identified in 48 patients: 21 had t(8;21) or its variant and AML1/ETO, and 27 had inv(16)/t(16;16), CBFbeta/MYH11, or both. Initial cytogenetic and RT-PCR analyses correctly classified 95.7% and 96.1% of patients, respectively (P =.83). Initial cytogenetic results were considered to be false-negative in three AML1/ETO-positive patients with unique variants of t(8;21), and in three CBFbeta/MYH11-positive patients with, respectively, an isolated +22; del(16)(q22),+22; and a normal karyotype. The latter three patients were later confirmed to have inv(16)/t(16;16) cytogenetically. Only one of 124 patients reported initially as cytogenetically normal was ultimately RT-PCR-positive. There was no false-positive cytogenetic result. Initial RT-PCR was falsely negative in two patients with inv(16) and falsely positive for AML1/ETO in two and for CBFbeta/MYH11 in another two patients. Two patients with del(16)(q22) were found to be CBFbeta/MYH11-negative. M4Eo marrow morphology was a good predictor of the presence of inv(16)/t(16;16).
  
  
  CONCLUSIONS
  Patients with t(8;21) or inv(16) can be successfully identified in prospective multi-institutional clinical trials. Both cytogenetics and RT-PCR detect most such patients, although each method has limitations. RT-PCR is required when the cytogenetic study fails; it is also required to determine whether patients with suspected variants of t(8;21), del(16)(q22), or +22 represent CBF AML. RT-PCR should not replace cytogenetics and should not be used as the only diagnostic test for detection of CBF AML because of the possibility of obtaining false-positive or false-negative results.
authors.affiliation: Division of Hematology and Oncology, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210-1228, USA. mrozek-1@medctr.osu.edu
authors.forename: K
authors.initials: K
authors.lastname: Mrózek
authors.forename: T W
authors.initials: TW
authors.lastname: Prior
authors.forename: C
authors.initials: C
authors.lastname: Edwards
authors.forename: G
authors.initials: G
authors.lastname: Marcucci
authors.forename: A J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: P J
authors.initials: PJ
authors.lastname: Snyder
authors.forename: P R
authors.initials: PR
authors.lastname: Koduru
authors.forename: K S
authors.initials: KS
authors.lastname: Theil
authors.forename: M J
authors.initials: MJ
authors.lastname: Pettenati
authors.forename: K J
authors.initials: KJ
authors.lastname: Archer
authors.forename: M A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: J W
authors.initials: JW
authors.lastname: Vardiman
authors.forename: J E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: R A
authors.initials: RA
authors.lastname: Larson
authors.forename: C D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000328:Adult; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; D014157:Transcription Factors