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Phenotypic and genotypic infidelity in B-lineage neoplasms, including transdifferentiation following targeted therapy: Report from the 2021 SH/EAHP Workshop

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AMERICAN JOURNAL OF CLINICAL PATHOLOGY
卷 159, 期 6, 页码 538-553

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OXFORD UNIV PRESS INC
DOI: 10.1093/ajcp/aqad035

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B-cell acute lymphoblastic leukemia; acute myeloid sarcoma; lineage infidelity; transdifferentiation; targeted therapy

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Session 2 of the 2021 Society for Hematopathology and European Association for Haematopathology Workshop presented examples of lineage infidelity and transdifferentiation in B-lineage neoplasms, including after targeted therapy. A total of 20 cases were examined, with whole-exome sequencing and genome-wide RNA expression analysis conducted on a subset. The findings demonstrated lineage switch to acute myeloid leukemia or mixed-phenotype acute leukemia in multiple cases of B-cell acute lymphoblastic leukemia (B-ALL) upon relapse, as well as changes in maturational state without lineage switch. Aberrant T-cell antigen expression was also observed in mature B-cell lymphoma cases, with correlations to alterations in tumor cell gene expression patterns.
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.

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