title: Clonality profile in relapsed precursor-B-ALL children by GeneScan and sequencing analyses. Consequences on minimal residual disease monitoring.
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.
authors.affiliation: Laboratorio di Emato Oncologia, Dipartimento di Pediatria, Universita' di Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Germano
authors.forename: L
authors.initials: L
authors.lastname: del Giudice
authors.forename: S
authors.initials: S
authors.lastname: Palatron
authors.forename: E
authors.initials: E
authors.lastname: Giarin
authors.forename: G
authors.initials: G
authors.lastname: Cazzaniga
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: G
authors.initials: G
authors.lastname: Basso
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D012008:Recurrence; D017422:Sequence Analysis, DNA; D013997:Time Factors