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Oncology. 2012;83(3):128-34. doi: 10.1159/000338769. Epub 2012 Jul 18.

Rearrangement of the myeloid/lymphoid leukemia gene in therapy-related myelodysplastic syndrome in patients previously treated with agents targeting DNA topoisomerase II.

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  • 1Department of Clinical Pathology, South Egypt Cancer Institute, Assiut, Egypt.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

It is proposed that the MLL gene is etiopathogenetically relevant for hematological neoplasias transformation and survival.

Copyright © 2012 S. Karger AG, Basel.

PMID:
22814291
[PubMed - indexed for MEDLINE]
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