Clonal cytopenia of undetermined significance (CCUS)-associated reversion of donor-derived, transient αβ T-cell large granular clonal lymphocytosis, emerging post-transplant in a patient with a history of γδ T-cell large granular lymphocytic leukemia.

Autor:	El Hussein S; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA; elhusseinsiba@gmail.com zoltan_oltvai@urmc.rochester.edu., Evans AG; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA., Fitzsimmons JM; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA., Leong N; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA., Buldo M; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA., Segal JP; Department of Pathology, University of Chicago Medicine, Chicago, Illinois 60637, USA., Jajosky AN; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA., Rothberg PG; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA., Liesveld JL; Department of Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA.; The Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York 14642, USA., Oltvai ZN; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA; elhusseinsiba@gmail.com zoltan_oltvai@urmc.rochester.edu.
Jazyk:	angličtina
Zdroj:	Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2023 May 09; Vol. 9 (2). Date of Electronic Publication: 2023 May 09 (Print Publication: 2023).
DOI:	10.1101/mcs.a006241
Abstrakt:	Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) has revolutionized the therapy of hematolymphoid malignancies. Yet, how to best detect or predict the emergence of HSCT-related complications remain unresolved. Here, we describe a case of donor-derived, transient Alpha Beta (αβ) T-cell large granular clonal lymphocytosis and cytopenia that emerged post-HSCT in a patient with a history of gamma delta (γδ) T-cell large granular lymphocytic leukemia (T-LGLL). Clonal unrelatedness of post-transplant T-LGL lymphocytosis to the patient's pretransplant T-LGLL was first identified by T-cell receptor (TCR) PCR showing different sized fragments of rearranged gamma chains, in addition to shift from γδ to αβ TCR expression by flow cytometry analyses. Donor-derivation of the patient's post-transplant clonal lymphocytosis was confirmed by serial chimerism analyses of recipient's blood specimens demonstrating 100% donor DNA. Moreover, oncogenic DNMT3A and RUNX1 mutations were detected by next-generation sequencing (NGS) only in post-transplant specimens. Intriguingly, despite continued increase in DNMT3A and RUNX1 mutation load, the patient's clonal lymphocytosis and anemia eventually largely resolved; yet, the observed mutation profile with persistent thrombocytopenia indicated secondary clonal cytopenia of undetermined significance (CCUS) in the absence of overt morphologic evidence of myeloid neoplasm in the marrow. This case illustrates the utility of longitudinal chimerism analysis and NGS testing combined with flow cytometric immunophenotyping to evaluate emerging donor-derived hematolymphoid processes and to properly interpret partial functional engraftment. It may also support the notion that driver mutation-induced microenvironmental changes may paradoxically contribute to reestablishing tissue homeostasis. (© 2023 El Hussein et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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