Comparative analysis of Ig and TCR gene rearrangements at diagnosis and at relapse of childhood precursor-B-ALL provides improved strategies for selection of stable PCR targets for monitoring of minimal residual disease
| Autor: | MJ Willemse, Elisabeth R. van Wering, Mirjam van der Burg, Jacques J.M. van Dongen, Tomasz Szczepański, Bas Brinkhof |
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| Přispěvatelé: | Immunology |
| Rok vydání: | 2002 |
| Předmět: |
Immunology
Immunoglobulins Biology Gene Rearrangement T-Lymphocyte Biochemistry Polymerase Chain Reaction Bone Marrow Recurrence hemic and lymphatic diseases Acute lymphocytic leukemia medicine Secondary Acute Myeloid Leukemia Humans Child B cell Gene Rearrangement T-cell receptor Cell Biology Hematology Gene rearrangement medicine.disease Minimal residual disease Burkitt Lymphoma Leukemia medicine.anatomical_structure Monoclonal Precancerous Conditions |
| Zdroj: | Blood, 99, 2315-2323. American Society of Hematology |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements are excellent patient-specific polymerase chain reaction (PCR) targets for detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL), but they might be unstable during the disease course. Therefore, we performed detailed molecular studies in 96 childhood precursor-B‐ ALL at diagnosis and at relapse (n 5 91) or at presumably secondary acute myeloid leukemia (n 5 5). Clonal Ig and TCR targets for MRD detection were identified in 94 patients, with 71% of these targets being preserved at relapse. The best stability was found for IGK-Kde rearrangements (90%), followed by TCRG (75%), IGH (64%), and incomplete TCRD rearrangements (63%). Combined Southern blot and PCR data for IGH, IGK-Kde, and TCRD genes showed significant differences in stability at relapse between monoclonal and oligoclonal rearrangements: 89% versus 40%, respectively. In 38% of patients all MRD-PCR targets were preserved at relapse, and in 40% most of the targets (> 50%) were preserved. In 22% of patients most targets (10 cases) or all targets (10 cases) were lost at relapse. The latter 10 cases included 4 patients with secondary acute myeloid leukemia with germline Ig/TCR genes. In 5 other patients additional analyses proved the clonal relationship between both disease stages. Finally, in 1 patient all Ig/TCR gene rearrangements were completely different between diagnosis and relapse, which is suggestive of secondary ALL. Based on the presented data, we propose stepwise strategies for selection of stable PCR targets for MRD monitoring, which should enable successful detection of relapse in most (95%) of childhood precursor-B‐ALL. (Blood. 2002;99:2315-2323) |
| Databáze: | OpenAIRE |
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