Karyotypic analysis in a 2-year-old boy who presented with M5a AML and relapsed 6 years later with the same translocation in precursor-B ALL. FISH for the MLL gene demonstrates a positive/rearranged result. This single-interphase nucleus shows the typical abnormal signal pattern for the MLL break-apart FISH probe. The abnormal MLL allele is identified by the distinctly separate (broken apart) orange and green signals (yellow arrow). In contrast, the remaining second MLL allele shows a normal fusion pattern of overlapping green and orange signals. Inset shows a selected G-banded karyotype demonstrating an abnormal karyotype; 46,XY,del(6)(q13),t(9;11)(p22;q23). The translocation involves a reciprocal exchange of genomic material on chromosomes 9 and 11. As a consequence of this translocation, the MLL gene localized to 11q23 is juxtaposed to the MLLT3 gene on 9p22, resulting in an oncogenic chimeric fusion gene. The translocation has been associated with IGSF4 overexpression that is partially regulated by promoter methylation.19 (Images courtesy of Dr. Kaaren Reichard.)
