title: Amplification of the AML1(CBFA2) gene on ring chromosomes in a patient with acute myeloid leukemia and a constitutional ring chromosome 21.
abstract: In the genesis of hematologic neoplasms gene amplification is a mechanism for illegitimate activation of proto-oncogenes. We report a phenotypically normal patient with a constitutional ring chromosome 21 who developed acute myeloid leukemia (AML). The leukemic cells revealed size-variable ring chromosomes 21 with amplification of the proto-oncogene AML1, located in the chromosomal band 21q22, within the rings. Hitherto, amplification of the proto-oncogene AML1-also in form of a ring chromosome-has been described recently only in one patient with myelodysplastic syndrome (MDS). In AML, gene amplification by ring formation has been demonstrated only in another three patients (amplification of the MLL gene in two cases and of the ETV6 gene in one case). Here we present the new evidence that the internal rearrangement of a constitutional ring chromosome 21 resulted in multiplication of a proto-oncogene in bone marrow cells and provided obviously a selective growth advantage. Moreover the amplification of ribosomal DNA was observed in the ring chromosomes of the tumor cells.
authors.affiliation: Institut für Medizinische Biologie der Universität Wien, Währinger Strasse 10, 1090, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Streubel
authors.forename: P
authors.initials: P
authors.lastname: Valent
authors.forename: K
authors.initials: K
authors.lastname: Lechner
authors.forename: C
authors.initials: C
authors.lastname: Fonatsch
mesh_terms: D000208:Acute Disease; D000328:Adult; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012303:Ring Chromosomes; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D014157:Transcription Factors