Topoisomerase II inhibitors ; Secondary hematologic malignancy ; MLL gene
Abstract
Background :It has become apparent that the MLL (myeloid-lymphoid leukemia or mixed-lineage leukemia) gene is frequently rearranged in patients with secondary leukemia or myelodysplasia associated with chemotherapeutic regimens including topoisomerase II inhibitors (topo II inhibitors). Few studies have been reported on hematological or chromosomal abnormalities associated with topo II inhibitor therapy in Korea. We report three cases with topo II inhibitor therapy-related 11q23 abnormalities. First, a 10-year old female with a therapy-related chromosomal abnormality t(11;16) (q23;p13.3) without bone marrow abnormalities; second, a 67-year old male with therapy-related myelodysplastic syndrome (MDS) with add(11)(q23) and advanced to acute myeloid leukemia with t(2;11)(p23;q23) within a year; and third, a 42-year old male with therapy-related acute myeloid leukemia (AML) with 11q23 abnormality demonstrated by fluorescence in situ hybridization (FISH) analysis using a MLL gene probe and which later proved to be t(9;11)(p22;q23). The chemotherapeutic agents for the primary malignancies (ovarian primitive neuroectodermal tumor, PNET; squamous lung cell carcinoma; and Ewing`s sarcoma/PNET, respectively) consisted of topo II inhibitiors as well as alkylating agents. The latent periods from primary therapy to identification of 11q23 abnormalities were relatively short at 9 months, 35 months, and 22 months, respectively. Patients treated with topo II inhibitors are at risk for developing secondary MDS or leukemia that has distinct features from those associated with alkylating agents. The genetic basis and optimal treatment for clonal changes from topo II inhibitor therapy remain to be determined. A close follow-up of cytogenetic and/or FISH study with a MLL gene probe for patients with a history of topo II inhibitor treatment would be very useful for diagnosis and prediction of secondary hematologic malignancies.