title: The TEL-AML1 real-time quantitative polymerase chain reaction (PCR) might replace the antigen receptor-based genomic PCR in clinical minimal residual disease studies in children with acute lymphoblastic leukaemia.
abstract: Prospective studies in children with B-precursor acute lymphoblastic leukaemia (ALL) have shown that polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) using immunoglobin (Ig) and T-cell receptor (TCR) gene rearrangements as targets can be used to identify patients with a high relapse risk. The disadvantage of this approach is that for each patient preferably two different targets have to be identified. The t(12;21)(p13;q22) with the TEL-AML1 fusion gene is present in approximately 25% of children with B-precursor ALL. In these patients, sensitive reverse transcription (RT)-PCR analysis of the TEL-AML1 fusion transcript might be a more simple and less laborious alternative approach. However, it is unknown how stable the mRNA is and whether the number of transcripts per leukaemic cell remains constant during follow-up. We investigated whether the MRD results obtained using RT-PCR of TEL-AML1 transcripts correlated with the clinically validated genomic PCR for Ig and TCR gene rearrangements. Therefore, we used real-time quantitative (RQ)-PCR analysis for both types of targets and assessed the MRD levels in 36 follow-up bone marrow samples (obtained during the first 1.5 years after diagnosis) from 13 patients with B-precursor ALL. In 34/36 bone marrow samples the Ig/TCR RQ-PCR and TEL-AML1 RQ-PCR revealed equal levels of MRD and these results had a strong correlation (P < 0.0001, R2 = 0.84). Therefore, we conclude that the TEL-AML1 RQ-PCR can, in principle, replace Ig/TCR RQ-PCR in B-precursor ALL with t(12;21).
authors.affiliation: Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: de Haas
authors.forename: W B
authors.initials: WB
authors.lastname: Breunis
authors.forename: R
authors.initials: R
authors.lastname: Dee
authors.forename: O J H M
authors.initials: OJ
authors.lastname: Verhagen
authors.forename: W
authors.initials: W
authors.lastname: Kroes
authors.forename: E R
authors.initials: ER
authors.lastname: van Wering
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: H
authors.initials: H
authors.lastname: van den Berg
authors.forename: C E
authors.initials: CE
authors.lastname: van der Schoot
mesh_terms: D002648:Child; D003199:Computer Systems; D050676:Core Binding Factor Alpha 2 Subunit; D005500:Follow-Up Studies; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D016014:Linear Models; D018365:Neoplasm, Residual / Q000175:diagnosis*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis*; D012333:RNA, Messenger / Q000032:analysis*; D012680:Sensitivity and Specificity; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein