Complex Translocation (8;16;21); a New Variant of t(8;21), with t(13;22) in Acute Myeloid Leukemia.

The translocation (8;21)(q22;q22) is a common recurrent chromosome aberration present in 10% to 15% of all acute myeloid leukemias. In approximately 3% of all cases with t(8;21), a variant of t(8;21) involving chromosomes 8,21 and other chromosomes is present. We report here a case of AML-M2 with a new complex translocation (8;16;21)(q22;p16.3;q22) associated with additional abnormality t(13;22)(q22;q13) not described before. Fluorescent in-situ hybridization analysis with probes for ETO and AML1 genes, and probes for the subtelomeric regions of chromosome 16 demonstrated an ETO-AML1 fusion signal on der(8). The 5′ region of ETO gene with chromosome arm distal to translocation breakpoint had moves to der(16) while region of AML1 probe proximal to translocation brealpoint stayed on der(21). The signal for the subtelomeric probe for 16p was present on der(21). Use of painting probe for chromosome 13 confirmed t(13;22). In a hematopoietic cell the expression of chimeric AML1- ETO protein resulting from t(8;21) plays a key role in leukemic transformation by targeting AML1-CBFB transcription factor complex, an essential regulator of genes required for normal hematopoietic cell development, by dominant negative effect on normal AML1 protein. However, the expression of AML1- ETO does not block normal differentiation of stem cells. Additional mutational events must occur in hematopoietic progenitor cell to block normal path of differentiation. Although clinical features of variant translocation is same as cases with conventional t(8;21), prognostic implications of variant (8;21) are yet to be established. Chromosome region 16p13 has been involved in clinically important translocations with poor prognosis such as t(8;16)(p11;p13) and t(11;16)(q23;p13) and may have similar implications. Translocation (8;21) is frequently accompanied by additional chromosome abnormalities i.e. loss of sex chromosome, trisomy 8 and structural abnormalities of 9q. Additional reports on secondary genetic alterations accompanying t(8;21) are needed to understand their cumulative effect. Chromosome region 16p13, 13q22 and 22q13 may harbor putative genes influencing normal path of differentiation.