Monitoring of childhood ALL using BCR-ABL1 genomic breakpoints identifies a subgroup with CML-like biology
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
28331056
DOI
10.1182/blood-2016-11-749978
PII: S0006-4971(20)33376-0
Knihovny.cz E-resources
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma blood genetics MeSH
- Fusion Proteins, bcr-abl genetics MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood genetics MeSH
- Gene Deletion MeSH
- Child MeSH
- Genome, Human * MeSH
- Hematopoiesis MeSH
- Humans MeSH
- Adolescent MeSH
- Leukocyte Count MeSH
- Child, Preschool MeSH
- Receptors, Antigen, T-Cell genetics MeSH
- Neoplasm, Residual genetics MeSH
- Ikaros Transcription Factor genetics MeSH
- Treatment Outcome MeSH
- Chromosome Breakage * MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Fusion Proteins, bcr-abl MeSH
- IKZF1 protein, human MeSH Browser
- Receptors, Antigen, T-Cell MeSH
- Ikaros Transcription Factor MeSH
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
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
References provided by Crossref.org
Distinct pattern of genomic breakpoints in CML and BCR::ABL1-positive ALL: analysis of 971 patients