RESUMEN
The t(8;21)/RUNX1-RUNX1T1 is found in ~5 percent of cases of acute myeloid leukemia (AML) and in 10 percent of the prior AML with maturation (M2) category of the French-American-British (FAB) classification. While AML with t(8;21) is considered a distinct entity with a favorable prognosis, the clinical consequence of variant translocations is less well defined. In this report we described a 45 year-old male patient having a diagnosis of AML-M2 with morphologic and immunophenotypic features suggestive of t(8;21). However, the initial karyotypic analysis revealed an apparently balanced translocation between 1p36 and 8q22. Further fluorescence in situ hybridization (FISH) studies using the AML1/ETO and the p58 probes from Abbott Molecular, demonstrated a three-way translocation between chromosomes 1, 21, and 8, with single fusion of RUNX1-RUNX1T1 on the derivative chromosome 8 [t(1;21;8)(p36.1;q22;q22)]. The patient was in complete remission after induction therapy followed by consolidation. This report demonstrates the importance of FISH studies for detection of cryptic specific chromosome rearrangements that may have prognostic significance.
RESUMEN
The t(8;21) accounts for 5-12% of AML patients, often occurring in the younger population (1). This translocation fuses the AML 1 gene on chromosome 21q22 and the ETO gene on 8q22 resulting in a AML1-ETO hybrid transcript. Under the World Health Organization (WHO) classification, the t(8;21) is distinctly characterized under AML with recurrent aberrations with a favorable prognosis. Variant t(8;21; var) display comparable clinical manifestations compared to the classical translocation; however, they are less defined and their clinicak significance remains arguable. Complex t(8;21) variants account fo approximately 3-4% of all AML1-ETO fusion transcripts with approximately 100 variants described in the literature (1,2). In this article, we discuss a variant (8;21) translocation in AML. Chromosomal analysis of this case using conventional cytogenetics showed an apparently balanced transcolation between the short arm of chromosome 1 at 1p36 and the long arm of chromosome 8 at 8q22. Subsequent FISH studies demonstrated that there was also a fusion of the AML1 and ETO genes on the derivative chromosome 8, a key event in M2, a small ETO signal on chromosome 1, a normal ETO signal on the other homologue 8 and two AML1 signals (a small AML1 signal on the normal copy of chromosome 21). This report demonstrates how important is to do FISH studies to characterize a specific rearrangement in the management of hematological maligancies.
La translocación (8;21) se presenta en un 5-12% de casos de leucemia mieloide aguda y ocurre preponderamente en una población joven de estos pacientes. En esta translocación se fusionan los genes AML1 en el cromosoma 21q22 con el gen ETO en el cromosoma 8 en el locus 8q22 produciendo un gen híbrido AML1-ETO, el cual esta asociado a un pronóstico bastante favorable. En este artículo presentamos un paciente cuyo cariotipo, usando citogenética convencional, mostró una "translocación aparentemente balanceada" entre el brazo corto del cromosoma 1 en la banda 1p36 y el brazo largo del cromosoma 8 en la banda 8q22. Los estudios de FISH usando la sonda de dos colores y doble fusión AML1/ETO determinaron que se trataba de una translocación triple entre los cromosomas 1, 8 y 21 ya que se pudo observar una fusión AML1/ETO el cromosoma 8 derivado, el cual es el evento clave en la translocación típica (8;21). Se observó además una señal de AML1 pequeña en el cromosoma derivado 21, una copia normal completa de AML1 en el homólogo normal 21, una señal pequeña de ETO en el brazo corto del cromosoma 1 así como una copia normal de ETO en el homólogo normal 8. El presente estudio nos permite ver la importancia de FISH en la caracterización de anormalidades cromosómicas así como el monitoreo de enfermedades hematológicas.