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Blood. 2017 May 18;129(20):2771-2781. doi: 10.1182/blood-2016-11-749978. Epub 2017 Mar 22.

Monitoring of childhood ALL using BCR-ABL1 genomic breakpoints identifies a subgroup with CML-like biology.

Author information

1
Childhood Leukemia Investigation Prague (CLIP) and.
2
Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
3
University Hospital Motol, Prague, Czech Republic.
4
Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
5
Department of Pediatrics, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany.
6
Gennet, Center for Fetal Medicine and Reproductive Genetics, Prague, Czech Republic.
7
Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
8
Blood and Marrow Transplant Services, Children's Hospital at Westmead, Sydney, NSW, Australia; and.
9
School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.

Abstract

We used the genomic breakpoint between BCR and ABL1 genes for the DNA-based monitoring of minimal residual disease (MRD) in 48 patients with childhood acute lymphoblastic leukemia (ALL). Comparing the results with standard MRD monitoring based on immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements and with quantification of IKZF1 deletion, we observed very good correlation for the methods in a majority of patients; however, >20% of children (25% [8/32] with minor and 12.5% [1/8] with major-BCR-ABL1 variants in the consecutive cohorts) had significantly (>1 log) higher levels of BCR-ABL1 fusion than Ig/TCR rearrangements and/or IKZF1 deletion. We performed cell sorting of the diagnostic material and assessed the frequency of BCR-ABL1-positive cells in various hematopoietic subpopulations; 12% to 83% of non-ALL B lymphocytes, T cells, and/or myeloid cells harbored the BCR-ABL1 fusion in patients with discrepant MRD results. The multilineage involvement of the BCR-ABL1-positive clone demonstrates that in some patients diagnosed with BCR-ABL1-positive ALL, a multipotent hematopoietic progenitor is affected by the BCR-ABL1 fusion. These patients have BCR-ABL1-positive clonal hematopoiesis resembling a chronic myeloid leukemia (CML)-like disease manifesting in "lymphoid blast crisis." The biological heterogeneity of BCR-ABL1-positive ALL may impact the patient outcomes and optimal treatment (early stem cell transplantation vs long-term administration of tyrosine-kinase inhibitors) as well as on MRD testing. Therefore, we recommend further investigations on CML-like BCR-ABL1-positive ALL.

PMID:
28331056
DOI:
10.1182/blood-2016-11-749978
[Indexed for MEDLINE]
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