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.

Blood and Marrow Transplant Services Children's Hospital at Westmead Sydney NSW Australia; and

Childhood Leukemia Investigation Prague and

Children's Cancer Institute Lowy Cancer Research Centre University of New South Wales Sydney NSW Australia

Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Pediatrics University Medical Centre Schleswig Holstein Campus Kiel Kiel Germany

Gennet Center for Fetal Medicine and Reproductive Genetics Prague Czech Republic

Institute of Hematology and Blood Transfusion Prague Czech Republic

School of Women's and Children's Health University of New South Wales Sydney NSW Australia

University Hospital Motol Prague Czech Republic

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Blood. 2017 May 18;129(20):2713-2714. doi: 10.1182/blood-2017-04-776369. PubMed

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