Concurrent translocations of MLL and CBFA2 (AML1) genes with new partner breakpoints in a child with secondary myelodysplastic syndrome after treatment of acute lymphoblastic leukemia.

The MLL gene at 11q23 is frequently disrupted by chromosomal translocations in de novo acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), and in secondary leukemia induced by treatment with inhibitors of topoisomerase II, including the epipodophylotoxins. The CBFA2 gene at 21q22 is also frequently disrupted in de novo ALL and AML and less commonly in secondary AML. Rearrangements of MLL and CBFA2 have been described in de novo and secondary myelodysplastic syndrome (MDS). There have been no previous descriptions of coexisting abnormalities of MLL and CBFA2 in cases of MDS or acute leukemia. We describe a patient who developed secondary MDS after chemotherapy for hyperdiploid ALL. At the time of conversion to MDS, the patient had 46 chromosomes, with an 11q23/MLL translocation involving a new partner breakpoint at 2p23 and a 21q22/CBFA2 translocation involving a new partner breakpoint at 6p22. This report is the first to describe new partner breakpoints at 2p23 and 6p22 for MLL and CBFA2 genes, respectively, and concurrent rearrangements of these genes in a patient with secondary MDS.