Rearrangement of the Myeloid/Lymphoid Leukemia Gene in Therapy-Related Myelodysplastic Syndrome in Patients Previously Treated with Agents Targeting DNA Topoisomerase II
- 18 July 2012
- journal article
- Published by S. Karger AG in Oncology
- Vol. 83 (3), 128-134
- https://doi.org/10.1159/000338769
Abstract
Therapy-related acute myeloid leukemias (t-AML), with balanced translocations affecting the 11q23 point in the myeloid/lymphoid leukemia (MLL) gene, are one of the most serious complications of treatments with topoisomerase II inhibitors. However, only a few reports of t-AML exist. We aimed to study if these translocations are cumulative-dose-dependent, their frequency in therapy-related myelodysplastic syndrome and the relationship between their presence, the type of therapy and the response criteria. This retrospective study included 120 patients with various malignancies (108 non-Hodgkin's lymphoma, 8 Hodgkin's disease and 4 neuroblastoma) in remission, being treated with topoisomerase 2 inhibitors; 74 had been diagnosed with therapy-related myelodysplasia and 46 did not have dysplasia. All bone marrow biopsy samples were evaluated by fluorescence in situ hybridization for 11q23 point breakage in the MLL gene. MLL gene rearrangement frequency was 6% in dysplastic versus 2% in nondysplastic groups; p < 0.001. It was associated with a worse overall survival (mean 13 ± 2 vs. 39 ± 3 months, log-rank p value <0.0001). It was dose-dependent with a cut-off value of 290 mg/kg of topoisomerase II inhibitors as assessed by ROC curve (area under the curve 0.84 ± 0.05, p < 0.0001). It is proposed that the MLL gene is etiopathogenetically relevant for hematological neoplasias transformation and survival.Keywords
This publication has 31 references indexed in Scilit:
- Rearrangements of the MLL gene are influenced by DNA secondary structure, potentially mediated by topoisomerase II bindingGenes, Chromosomes and Cancer, 2009
- Does autologous transplantation directly increase the risk of secondary leukemia in lymphoma patients?Bone Marrow Transplantation, 2006
- Reduction From Seven to Five Cycles of Intensive Induction Chemotherapy in Children With High-Risk NeuroblastomaJournal of Clinical Oncology, 2004
- Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AMLLeukemia, 2003
- Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461)Blood, 2002
- Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001Leukemia, 2002
- Myelodysplastic syndromes in childhood: report of 49 patients from a French multicentre studyBritish Journal of Haematology, 1996
- Cytogenetics of secondary myelodysplasia (sMDS) and acute nonlymphocvtic leukemia (sANLL)European Journal of Haematology, 1991
- Secondary Acute Myeloid Leukemia in Children Treated for Acute Lymphoid LeukemiaNew England Journal of Medicine, 1989
- RISK OF THERAPY-RELATED LEUKAEMIA AND PRELEUKAEMIA AFTER HODGKIN'S DISEASE: Relation to Age, Cumulative Dose of Alkylating Agents, and Time from ChemotherapyThe Lancet, 1987