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Jan 18, 2019

34th BHS General Annual Meeting

MRD discrepancy during follow-up of p190 BCR-ABL1+ childhood B-ALL: diagnosis of a ‘CML-like’ ALL subgroup

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Abstract

Purpose A patient (M, 14 yr.) was diagnosed with B-ALL showing 92% lymphoid blasts and p190 BCR-ABL1 fusion transcript, and treated according to the EsphALL protocol with EORTC 58081+Glivec induction. Measurable residual disease (MRD) monitoring was performed by BCR-ABL1 qPCR, flow cytometry (FCM) for the detection of a leukemia-associated phenotype (LAIP) and a patient-tailored allele-specific oligonucleotide (ASO) qPCR. After six months, FCM and ASO-qPCR persistently showed negative MRD, in contrast to consistently high BCR-ABL1 copy number (CN) ratios (Fig.1). We here discuss the follow-up of a pediatric patient in an apparent state of remission with MRD discrepancy between BCR-ABL1 qPCR (positive) and ASO-qPCR/FCM (negative). Material and methods Molecular detection of the BCR-ABL1 fusion transcript was performed conform EAC guidelines. FCM detection of the LAIP CD38low/CD19+/CD10++/CD66c+/CD20- was performed on a FACSCanto II (BD) with instrument set-up and (pre-)analytical handlings according to EuroFlow guidelines. Two clonal targets (IGHV1-NL1*01-IGHJH6 and Vg8-Jg2.3) were defined as targets for ASO-qPCR set-up according to the Euro-MRD guidelines (sensitivity 10-4 and 10-5). Sorting was performed following bulk lysis and antibody staining (CD19/CD3/CD11b/CD14/CD33/CD45) on an Aria III sorter (BD). Results To investigate the biological basis of this discordancy, peripheral blood was examined 29 months post-diagnosis (BCR-ABL1/ABL1 CN ratio 4.94%) with sorting of different mature cell populations. The BCR-ABL1 fusion transcript was detected in neutrophils, monocytes, B-cells and T-cells with ratio’s 12.9%, 1.8%, 13.1% and 3.3%, respectively. This multilineage involvement implies that hematopoietic stem cells were most likely the cell of origin, as previously described by Hovorkova et al (Blood 2017), who defined a CML-like ALL subgroup that differs from typical ALL and CML. Conclusion The diagnosis of ‘CML-like’ BCR-ABL1+ ALL is suggested in case of MRD+/- discrepancy between BCR-ABL1 qPCR and ASO-qPCR/FCM, and may be confirmed by cell-sorting of the non-leukemic hematopoietic cells at remission.

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© Copyright 2019 Morressier GmbH.
All rights reserved.