Phenotypic and genotypic infidelity in B-lineage neoplasms, including transdifferentiation following targeted therapy: Report from the 2021 SH/EAHP workshop Review
| Authors: | Goodlad, J. R.; Xiao, W.; Amador, C.; Cook, J. R.; Happ, L.; Thakkar, D.; Dave, S.; Dogan, A.; Duffield, A.; Nejati, R.; Ott, G.; Wasik, M.; Czader, M. |
| Review Title: | Phenotypic and genotypic infidelity in B-lineage neoplasms, including transdifferentiation following targeted therapy: Report from the 2021 SH/EAHP workshop |
| Abstract: | OBJECTIVES: Session 2 of the 2021 Society for Hematopathology and European Association for Haematopathology Workshop collected examples of lineage infidelity and transdifferentiation in B-lineage neoplasms, including after targeted therapy. METHODS: Twenty cases were submitted. Whole-exome sequencing and genome-wide RNA expression analysis were available on a limited subsample. RESULTS: A diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) was rendered on at least 1 biopsy from 13 patients. There was 1 case of acute myeloid leukemia (AML); the remaining 6 cases were mature B-cell neoplasms. Targeted therapy was administered in 7 cases of B-ALL and 4 cases of mature B-cell neoplasms. Six cases of B-ALL underwent lineage switch to AML or mixed-phenotype acute leukemia at relapse, 5 of which had rearranged KMT2A. Changes in maturational state without lineage switch were observed in 2 cases. Examples of de novo aberrant T-cell antigen expression (n = 2) were seen among the mature B-cell lymphoma cohort, and their presence correlated with alterations in tumor cell gene expression patterns. CONCLUSIONS: This cohort of cases enabled us to illustrate, discuss, and review current concepts of lineage switch and aberrant antigen expression in a variety of B-cell neoplasms and draw attention to the role targeted therapies may have in predisposing neoplasms to transdifferentiation as well as other, less expected changes in maturational status. © The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. |
| Keywords: | genetics; leukemia, myeloid, acute; phenotype; acute lymphoblastic leukemia; targeted therapy; cell transdifferentiation; acute disease; acute myeloid leukemia; transdifferentiation; humans; human; b-cell acute lymphoblastic leukemia; precursor b-cell lymphoblastic leukemia-lymphoma; lineage infidelity; acute myeloid sarcoma |
| Journal Title: | American Journal of Clinical Pathology |
| Volume: | 159 |
| Issue: | 6 |
| ISSN: | 0002-9173 |
| Publisher: | Oxford University Press |
| Date Published: | 2023-06-01 |
| Start Page: | 538 |
| End Page: | 553 |
| Language: | English |
| DOI: | 10.1093/ajcp/aqad035 |
| PUBMED: | 37085149 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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