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Vol. 83, No. 3, 2012
Issue release date: August 2012
Section title: Clinical Study
Oncology 2012;83:128–134
(DOI:10.1159/000338769)

Rearrangement of the Myeloid/Lymphoid Leukemia Gene in Therapy-Related Myelodysplastic Syndrome in Patients Previously Treated with Agents Targeting DNA Topoisomerase II

Mosad E.a · Abdou M.b · Zaky A.H.c
Departments of aClinical Pathology and bMedical Oncology, South Egypt Cancer Institute, and cClinical Pathology Department, Faculty of Medicine, Assiut University, Assiut, Egypt

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Article / Publication Details

First-Page Preview
Abstract of Clinical Study

Received: 2/21/2012 11:35:54 AM
Accepted: 4/10/2012
Published online: 7/18/2012
Issue release date: August 2012

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 3

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL

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.

© 2012 S. Karger AG, Basel


  

Article Information

Received: February 21, 2012
Accepted after revision: April 10, 2012
Published online: July 18, 2012
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 3, Number of References : 30

  

Publication Details

Oncology (International Journal for Cancer Research and Treatment)

Vol. 83, No. 3, Year 2012 (Cover Date: August 2012)

Journal Editor: Markman M. (Philadelphia, Pa.)
ISSN: 0030-2414 (Print), eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL


Article / Publication Details

First-Page Preview
Abstract of Clinical Study

Received: 2/21/2012 11:35:54 AM
Accepted: 4/10/2012
Published online: 7/18/2012
Issue release date: August 2012

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 3

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL


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