title: Fusion gene transcripts and Ig/TCR gene rearrangements are complementary but infrequent targets for PCR-based detection of minimal residual disease in acute myeloid leukemia.
abstract: PCR-based monitoring of minimal residual disease (MRD) in acute leukemias can be achieved via detection of fusion gene transcripts of chromosome aberrations or detection of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements. We wished to assess whether both PCR targets are complementary in acute myeloid leukemia (AML). We investigated 105 consecutive AML cases for the presence of fusion gene transcripts by reverse transcriptase polymerase chain reaction (RT-PCR): AML1-ETO associated with t(8;21), CBFB-MYH11 with inv(16), PML-RARA with t(15;17), BCR-ABL with t(9;22), and MLL-AF4 with t(4;11). In 17 out of 105 AML cases (16%), fusion gene transcripts were found. Ninety-five of these AML patients (13 with fusion gene transcripts) were also investigated for the presence of IGH, IGK, TCRG and TCRD rearrangements by Southern blot and/or PCR heteroduplex analysis and sequencing. In nine out of 95 patients (9.5%), such rearrangements were found. Combined data revealed that only one patient with a fusion gene transcript had a coexistent Ig/TCR rearrangement. The nine AML patients with Ig/TCR rearrangements, as well as five additional AML patients from a previous study were investigated in more detail, revealing that Ig/TCR rearrangements in AML are immature and unusual. The presence of Ig/TCR rearrangements in AML did not correlate with RAG gene expression levels as determined by real-time quantitative PCR. In conclusion, fusion gene transcripts and Ig/TCR rearrangements are infrequent, but complementary MRD-PCR targets in AML.
authors.affiliation: Department of Immunology, Erasmus University Rotterdam/University Hospital Rotterdam, Rotterdam, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Boeckx
authors.forename: M J
authors.initials: MJ
authors.lastname: Willemse
authors.forename: T
authors.initials: T
authors.lastname: Szczepanski
authors.forename: V H J
authors.initials: VH
authors.lastname: van der Velden
authors.forename: A W
authors.initials: AW
authors.lastname: Langerak
authors.forename: P
authors.initials: P
authors.lastname: Vandekerckhove
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
mesh_terms: D000208:Acute Disease; D000328:Adult; D015139:Blotting, Southern; D002648:Child; D002869:Chromosome Aberrations; D017931:DNA Primers / Q000737:chemistry; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D015321:Gene Rearrangement; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D005803:Genes, Immunoglobulin / Q000235:genetics*; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics*; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics*; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers; D015342:DNA Probes; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C499311:RAG2 protein, human; D012333:RNA, Messenger; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein