Rearrangements of the MLL Gene in Therapy - Related Acute Myeloid Leukemia in Patients Previously Treated With Agents Targeting DNA - Topoisomerase

Chromosome band 1 1 q23 is frequently involved in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) de novo, as well as in myelodysplastic syndromes (MDS) and lymphoma. Five percent to 15% of patients treated with chemotherapy for a primary neoplasm develop therapy-related AML (t-AML) that may show rearrangements, usually translocations involving band 1 1 q23 or, less often, 21 q22. These leukemias develop after a relatively short latent period and often follow the use of drugs that inhibit the activity of DNA-topoisomerase II (topo 11). We previously identified a gene, MLL (myeloid-lymphoid leukemia or mixed-lineage leukemia), at 1 1 q23 that is involved in the de novo leukemias. We have studied 17 patients with t-MDS/t-AML, 12 of whom had cytogenetically detectable 1 1 q23 rearrangements. Ten of the 12 t-AML