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Childhood ALL

Clonality profile in relapsed precursor-B-ALL children by GeneScan and sequencing analyses. Consequences on minimal residual disease monitoring

Leukemia volume 17, pages 1573–1582 (2003)Cite this article

Abstract

Detection of minimal residual disease (MRD), using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements as clone-specific targets, represents the most recent development in diagnosis and treatment of acute lymphoblastic leukaemia (ALL). Nevertheless, risk of false-negative results, due to secondary or ongoing rearrangements of Ig/TCR genes during the disease course, might hamper MRD detection. Therefore, to gain extensive information on clonal stability, we performed PCR-GeneScan analysis of Ig/TCR gene rearrangements at diagnosis and subsequent relapse in bone marrow samples from 53 childhood precursor-B-ALL patients. In addition, sequencing analysis of junctional regions at diagnosis and relapse provided a detailed insight in the stability and changes of Ig/TCR gene rearrangements during the disease course. At least one stable clonal Ig/TCR target was found in 94% of patients. In three patients complete differences in Ig/TCR rearrangements between diagnosis and relapse were observed, suggesting relapse with a new clone. At relapse, 71% of diagnostic clonal PCR targets was conserved. Since the comparison of Ig/TCR gene rearrangements at diagnosis and relapse in our precursor-B-ALL patients did not show significant difference in the stability of different clonal PCR targets (IGH, 70%; IGK, 71%; TCRD, 67%; TCRG, 75%), we conclude that there is no ‘preferential’ clone-specific target for MRD monitoring.

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Acknowledgements

GG and LdG were equally responsible for designing the study and writing the paper; SP, EG, GC contributed to analysis and to revision of the results; GB and AB critically revised the manuscript and gave the final approval for its submission. GG and LdG gratefully acknowledge Dr Lucia De Zen, Dr Geertruy Te Kronnie for helpful comments and suggestions and Dr Sandra Trevisan for statistical analysis. This study was supported by CNR, Murst ex 60%, Fondazione Citta' della Speranza, Fondazione Tettamanti and Associazione Italiana Ricerca sul Cancro (AIRC).

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Authors and Affiliations

  1. Dipartimento di Pediatria, Laboratorio di Emato Oncologia, Universita' di Padova, Italy

    G Germano, L del Giudice, S Palatron, E Giarin & G Basso

  2. Centro Ricerca M Tettamanti, Clinica Pediatrica Universita' di Milano Bicocca, Ospedale San Gerardo, Monza, Italy

    G Cazzaniga & A Biondi

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  1. G Germano
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Appendix

Appendix

The following institutions enrolled patients in the study: Bari, Clinica Pediatrica I (Dr N Santoro); Bari, Clinica Pediatrica II (Professor N Rigillo); Bologna, Clinica Pediatrica (Professor G Paolucci, Dr A Pession); Brescia, Clinica Pediatrica (Professor L Notarangelo, Dr F Porto); Catanzaro, Div. di Ematologia (Professor S Magro); Firenze, Ospedale Meyer, Dipartimento di Pediatria, U. O. Oncoematologia Pediatrica (Professor G Bernini); Genova, Ist ‘G. Gaslini’ (Dr C Micalizzi); Modena, Clinica Pediatrica (Dr M Cellini); Monza, Clinica Pediatrica (Professor G Masera); Napoli, Ospedale Pausilipon (Professor V Poggi), Napoli, II Universita', Dipartimento di Pediatria, Servizio Autonomo di Oncologia Pediatrica (Professor MT Di Tullio); Padova, Clinica Pediatrica II (Professor L Zanesco); Parma, Clinica Pediatrica (Dr G Izzi); Pescara, Divisione di Ematologia (Dr A Di Marzio); Pisa, Clinica Pediatrica III (Dr C Favre); Torino, Clinica Pediatrica (Professor E Madon, Dr E Barison).

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Germano, G., del Giudice, L., Palatron, S. et al. Clonality profile in relapsed precursor-B-ALL children by GeneScan and sequencing analyses. Consequences on minimal residual disease monitoring. Leukemia 17, 1573–1582 (2003). https://doi.org/10.1038/sj.leu.2403008

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