title: The t(15;17) breakpoint in acute promyelocytic leukemia cluster within two different sites of the myl gene: targets for the detection of minimal residual disease by the polymerase chain reaction.
abstract: The retinoic acid receptor alpha (RAR alpha) and the myl gene are involved in the translocation breakpoint t(15;17)(q22;q21) in acute promyelocytic leukemia (APL). The majority of the breakpoint sites have been mapped within the second intron of the RAR alpha gene; however, the breakpoint sites on the myl gene are variable. Using primer sets derived from exon 2 or exon 3 of the RAR alpha gene and a primer derived from the myl cDNA, we were able to amplify the breakpoint sites of the fusion transcripts of all six APL RNA samples by the reverse transcriptase-polymerase chain reaction (RT-PCR). A DNA fragment of 290 bp (breakpoint A) was amplified using RNA samples from three patients, whereas two DNA fragments of 630 and 774 bp (breakpoint B) were amplified using RNA samples from the other three APL patients. DNA sequence analysis of the amplified fragments suggests that the APL breakpoints clustered within two different introns of the myl gene. Northern blot analysis demonstrated that fusion transcripts RAR alpha/myl and myl/RAR alpha of varying sizes were detected in patients with different breakpoint sites on the myl gene. In addition, we analyzed five APL samples in complete remission and detected t(15;17)-positive cells. We conclude that the t(15;17) breakpoints in APL can be amplified by PCR using a single primer set and that minimal residual disease can be demonstrated in APL using RT-PCR.
authors.affiliation: Hematopathology Program, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: K S
authors.initials: KS
authors.lastname: Chang
authors.forename: J F
authors.initials: JF
authors.lastname: Lu
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: J M
authors.initials: JM
authors.lastname: Trujillo
authors.forename: E
authors.initials: E
authors.lastname: Estey
authors.forename: A
authors.initials: A
authors.lastname: Cork
authors.forename: D T
authors.initials: DT
authors.lastname: Chu
authors.forename: E J
authors.initials: EJ
authors.lastname: Freireich
authors.forename: S A
authors.initials: SA
authors.lastname: Stass
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics; D002869:Chromosome Aberrations / Q000175:diagnosis*; D025063:Chromosome Disorders; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000235:genetics; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D009841:Oligonucleotides; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid