Chromosomal Abnormalities at 11q23 after Topoisomerase II Inhibitor Treatment: A Report of Three Cases / 대한임상병리학회지

ABSTRACT

It has become apparent that the MLL (myeloid-lymphoid leukemia or mixed-lineage leukemia) gene is frequently rearranged in patients with secondary leukemias or myelodysplasias 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 11q23 abnormalities associated with topo II inhibitor therapy. The first case was a 10-year-old female patient with t(11;16)(q23;p13.3) but without abnor-mal bone marrow findings. The second patient was a 67-year old male with therapy-related myelodys-plastic syndrome (MDS) with add(11)(q23), which evolved into acute myeloid leukemia with t(2;11) (p23;q23) after one year. The other patient was a 42-year-old male with a therapy-related acute myeloid leukemia with rearranged 11q23 demonstrated by fluorescence in situ hybridization (FISH) analysis using an MLL gene probe, which subsequently proved to be t(9;11)(p22;q23) by cytoge-netic analysis. The chemotherapeutic agents for the primary malignancies in the three patients (ovarian primitive neuroectodermal tumor, PNET; lung squamous cell carcinoma; and Ewing's sar-coma/ PNET, respectively) included topo II inhibitiors as well as alkylating agents. The periods from the primary therapy to the identification of 11q23 abnormalities were relatively short; 9 months, 35 months, and 22 months, respectively. Patients treated with topo II inhibitors are at risk for develop-ing secondary MDS and leukemia that have distinct features from those associated with alkylating agents. Although the genetic basis and optimal treatment for the clonal changes induced by topo II inhibitor therapy remain to be determined, a close follow-up with cytogenetic and/or MLL FISH study in patients with a history of topo II inhibitor treatment would be very useful for diagnosis and prediction of secondary hematologic malignancies.