Emergence of translocation t(9;11)-positive leukemia during treatment of childhood acute lymphoblastic leukemia
| Autor: | Reinald Repp, Silja Roettgers, Wolf D. Ludwig, Reiner Strick, Arndt Borkhardt, Markus Metzler, Pamela L. Strissel, J. D. Beck, Charlotte M. Niemeyer, Ursula Creutzig, Jochen Harbott, Thorsten Langer, Martin Schrappe, Dirk Reinhardt, Wolfgang Rascher, Martin Stanulla |
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| Rok vydání: | 2004 |
| Předmět: |
Oncology
Male Cancer Research medicine.medical_specialty Time Factors medicine.medical_treatment Chromosomal translocation Translocation Genetic Maintenance therapy hemic and lymphatic diseases Internal medicine Genetics medicine Humans Child Childhood Acute Lymphoblastic Leukemia Chemotherapy biology Reverse Transcriptase Polymerase Chain Reaction Topoisomerase Chromosomes Human Pair 11 Myeloid leukemia Infant Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Leukemia medicine.anatomical_structure DNA Topoisomerases Type II Child Preschool Immunology biology.protein Female Bone marrow Chromosomes Human Pair 9 |
| Zdroj: | Genes, chromosomescancer. 41(3) |
| ISSN: | 1045-2257 |
| Popis: | Therapy-related acute myeloid leukemia (t-AML) characterized by the t(9;11)(p22;q23) translocation is one of the most frequent secondary malignancies. The timing of the initiation of translocation and of development of the malignant t(9;11) clone during chemotherapy is presently unknown. In the present study, we backtracked bone marrow samples from three children during treatment for acute lymphoblastic leukemia (ALL). Two patients developed a t(9;11)-positive t-AML 19 and 30 months after therapy start, whereas the third patient, diagnosed with a rare t(9;11)-positive ALL, suffered from an ALL relapse 23 months after initial diagnosis. The genomic MLL-MLLT3 (MLL-AF9) fusion site was amplified by a multiplex, nested long-range PCR and used as a clonal marker for quantification of the MLL-MLLT3-positive cells during chemotherapy. The t(9;11)-positive clone was detectable 13 and 18 months after therapy start in both t-AML cases, which was 6-12 months before clinical diagnosis of the secondary malignancy. In the t(9;11)-positive ALL patient, the identical leukemic clone reoccurred during maintenance therapy after a short molecular remission, 8 months before clinically overt ALL relapse. The time course and characteristics of the genomic breakpoints in the present t-AML cases support the hypothesis of translocation formation as a result of defective breakage repair after topoisomerase II cleavage. |
| Databáze: | OpenAIRE |
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