Simple variant t(8;21) acute myeloid leukemias harbor insertions of the AML1 or ETO genes

• Published in: Genes chromosomes & cancer 1999-02, Vol.24 (2), p.165-171
• Main Authors: Taviaux, Sylvie, Brunel, Véronique, Dupont, Madeleine, Fernandez, Francisca, Ferraz, Concepcion, Carbuccia, Nadine, Sainty, Danielle, Demaille, Jacques, Birg, Françoise, Lafage-Pochitaloff, Marina
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Chromosomes, Human, Pair 12 - genetics; Chromosomes, Human, Pair 8 - genetics; Core Binding Factor Alpha 2 Subunit; Female; Humans; Leukemia, Myeloid, Acute - genetics; Male; Oncogene Proteins, Fusion; Recombinant Fusion Proteins - genetics; RUNX1 Translocation Partner 1 Protein; Transcription Factors - genetics; Translocation, Genetic - genetics
• ISSN: 1045-2257; 1098-2264
• DOI: 10.1002/(SICI)1098-2264(199902)24:2<165::AID-GCC12>3.0.CO;2-1

We report on the molecular characterization of two acute myeloid leukemias (AML), one AML‐M1 (patient 1) and one AML‐M2 (patient 2) with t(8;21)(p21;q22) and t(8;20)(q22;p13), respectively, at diagnosis. The locations of the breakpoints, 21q22 in patient 1 and 8q22 in patient 2, prompted us to search for a cryptic t(8;21)(q22;q22) and involvement of the AML1 and ETO genes. Dual‐color fluorescence in situ hybridization (FISH) using whole chromosome painting probes for chromosomes 8, 20, and 21 confirmed the conventional cytogenetic karyotypes. However, dual‐color FISH using appropriate ETO and AML1 probes disclosed an insertion of AML1 into 8q22 on the derivative chromosome 8 in patient 1 and of ETO into 21q22 on one chromosome 21 in patient 2, leading to AML1‐ETO fusion signals. Both cases expressed an AML1‐ETO transcript, shown by reverse transcriptase polymerase chain reaction and cDNA sequencing. Creation of functional AML1‐ETO fusion genes in these two simple variant t(8;21) probably occurred through complex mechanisms, combining translocation and insertion of chromosomal segments. Genes Chromosomes Cancer 24 :165–171, 1999. © 1999 Wiley‐Liss, Inc.