Myeloid leukemia after hematotoxins

Abstract

One of the most serious consequences of cancer therapy is the development of a second cancer, especially leukemia. Several distinct subsets of therapy-related leukemia can now be distinguished. Classic therapy-related myeloid leukemia typically occurs 5 to 7 years after exposure to alkylating agents and/or irradiation, has a myelodysplastic phase with trilineage involvement, and is characterized by abnormalities of the long arms of chromosomes 5 and/or 7. Response to treatment is poor, and allogenic bone marrow transplantation is recommended. Leukemia following treatment with agents that inhibit topoisomerase II, however, has a shorter latency, no preleukemic phase, a monoblastic, myelomonocytic, or myeloblastic phenotype, and balanced translocations, most commonly involving chromosome bands 11q23 or 21q22. The MLL gene at 11q23 or the AML1 gene at 21q22 are almost uniformly rearranged. MLL is involved with many fusion gene partners. Therapy-related acute lymphoblastic leukemia also occurs with 11q23 rearrangements. Therapy-related leukemias with 11q23 or 21q22 rearrangements, inv(16) or t(15;17), have a more favorable response to treatment and a clinical course similar to their de novo counterparts.