RESUMEN
Translocations involving the short arm of chromosome 12 are frequent events among patients with various hematologic malignancies. In approximately half of these patients, fluorescence in situ hybridization (FISH) analysis has shown that the breakpoints are clustered within the ETS-variant gene 6 (ETV6) at 12p13, leading to its fusion with a variety of partner genes on different chromosomes. The remaining patients have breakpoints centromeric or telomeric to ETV6 or, less frequently, interstitial 12p13 deletions that invariably involve this gene. In most cases reported, 12p translocations were found to be associated with other structural and/or numerical abnormalities as part of a complex karyotype. Initially using conventional cytogenetic analysis, we characterized the chromosomal breakpoints of three leukemia patients (two with B-acute lymphoblastic leukemia and one with myelodysplastic/myeloproliferative disorder) presenting a t(5;12)(q13;p13), t(12;15)(p13;q22), and dic(9;12)(p11;p11), respectively, as the only structural abnormalities in the karyotype. These rearrangements were further investigated using FISH and molecular studies. Two cases revealed cryptic three-way translocations that had gone undetected in the conventional cytogenetic analyses. One of the cases presented an ETV6 rearrangement with an unsuspected fusion, with the CBFA2 gene at 21q22. In the other two, small and large 12p deletions that included ETV6 were found. This report illustrates the chromosomal and molecular heterogeneity of rearrangements underlying 12p chromosome translocations in leukemia.
Asunto(s)
Cromosomas Humanos Par 12 , Proteínas de Unión al ADN/genética , Leucemia/genética , Proteínas Represoras/genética , Anciano , Fusión Artificial Génica , Niño , Rotura Cromosómica , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Proteínas Proto-Oncogénicas c-ets , Translocación Genética , Proteína ETS de Variante de Translocación 6RESUMEN
We report the results of cytogenetic, fluorescence in situ hybridization (FISH) and molecular analyses in a 15-year-old boy diagnosed with acute myeloid leukemia subtype M2 (AML-M2). Cytogenetic and FISH analyses, the latter with whole chromosome painting probes, revealed a complex translocation involving four chromosomes: t(8;17;15;21)(q22;q23;q15;q22). The observation of breakpoints at 8q22 and 21q22 suggested a rearrangement of the ETO and AML1 genes, respectively. Using a dual-color FISH test with ETO and AML1 probes, we demonstrated an AML1/ETO fusion signal on the derivative chromosome 8. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed the presence of AML1/ETO fusion transcripts identical to those found in classical t(8;21). The present case highlights the relevant role of the rearranged chromosome 8, which encodes the AML1/ETO fusion product in the pathogenesis of AML-M2.
Asunto(s)
Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 8/genética , Leucemia Mieloide Aguda/genética , Translocación Genética/genética , Adolescente , Cromosomas Humanos Par 15/genética , Cromosomas Humanos Par 7/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Humanos , Hibridación Fluorescente in Situ , Masculino , Proteínas de Fusión Oncogénica/genética , Proteína 1 Compañera de Translocación de RUNX1 , Factores de Transcripción/genéticaAsunto(s)
Fusión Artificial Génica , Proteínas de Unión al ADN/genética , Síndromes Mielodisplásicos/genética , Proteínas Represoras , Factores de Transcripción/genética , Neoplasias de la Mama/terapia , Carcinoma Lobular/terapia , Cromosomas Humanos Par 12 , Cromosomas Humanos Par 22 , Femenino , Humanos , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-ets , Translocación Genética , Proteína ETS de Variante de Translocación 6RESUMEN
We report a chronic myeloid leukemia patient without evidence of a Philadelphia (Ph) chromosome in whom RT-PCR analysis performed in blast crisis demonstrated the existence of both common b3a2 and b2a2 BCR/ABL fusion transcripts. In situ hybridization studies with BCR- and ABL-specific probes showed location of the BCR/ABL fusion gene on chromosome 9, band q34, instead of at chromosome 22q11, and that it resulted from an insertion of the 5' side of BCR within the ABL gene on chromosome 9. The vast majority of cells showed a BCR/ABL fusion gene on both chromosomes 9, which is equivalent to a double Ph chromosome, thus reinforcing the notion that the critical event in CML is the formation of a functional BCR/ABL fusion gene.