Analysis of IG/TCR gene rearrangements in Swedish childhood acute lymphoblastic leukemia diagnosed 2002-2006: a multi-centre study supporting the applicability of real-time-PCR for minimal residual disease assessment
(English)Manuscript (Other academic)
Minimal residual disease (MRD) detection during the early treatment phase has become an important stratification parameter in many childhood acute lymphoblastic leukemia (ALL) treatment protocols. Here we aimed to address the applicability of real-time quantitative polymerase chain reaction (RQ-PCR) of rearranged antigen receptor genes as an MRD method in a multi-centre setting. From a Swedish population-based cohort of 334 ALL cases diagnosed during 2002-2006, we analysed 279 diagnostic samples (84%) by screening for rearranged immunoglobulin (IG) and T-cell receptor (TCR) genes. Allele-specific oligonucleotides were designed for each patient rearrangement, and the sensitivity and quantitative level was determined for each target. The analyses were performed at five different centres while interpretation of the results was performed at consensus meetings. Overall, clonal IG/TCR rearrangements were detected in 97% (236/244) of B-cell precursor ALL (BCP ALL) and 94% (33/35) of T-ALL. A sensitive RQ-PCR analysis (≤ 10-4) was obtained in 89% (216/244) of BCP ALL and in 74% (26/35) of T-ALL. With the stratification threshold of ≥10-3 for identification of high-risk patients, 93% of BCP ALL and 86% of T-ALL reached this quantitative range by at least one target gene. Taken together, this national multi-centre study supports the use of RQ-PCR analysis as a robust method for MRD detection in the majority of childhood ALL cases.
RQ-PCR, rearranged IG/TCR genes, minimal residual disease, childhood acute lymphoblastic leukemia
IdentifiersURN: urn:nbn:se:uu:diva-100936OAI: oai:DiVA.org:uu-100936DiVA: diva2:211569