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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

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 (α...

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Autores principales: El Hussein, Siba, Evans, Andrew G., Fitzsimmons, John M., Leong, Nufatt, Buldo, Meghan, Segal, Jeremy P., Jajosky, Audrey N., Rothberg, Paul G., Liesveld, Jane L., Oltvai, Zoltán N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10240839/
https://www.ncbi.nlm.nih.gov/pubmed/37160316
http://dx.doi.org/10.1101/mcs.a006241
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author El Hussein, Siba
Evans, Andrew G.
Fitzsimmons, John M.
Leong, Nufatt
Buldo, Meghan
Segal, Jeremy P.
Jajosky, Audrey N.
Rothberg, Paul G.
Liesveld, Jane L.
Oltvai, Zoltán N.
author_facet El Hussein, Siba
Evans, Andrew G.
Fitzsimmons, John M.
Leong, Nufatt
Buldo, Meghan
Segal, Jeremy P.
Jajosky, Audrey N.
Rothberg, Paul G.
Liesveld, Jane L.
Oltvai, Zoltán N.
author_sort El Hussein, Siba
collection PubMed
description 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.
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spelling pubmed-102408392023-06-06 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 El Hussein, Siba Evans, Andrew G. Fitzsimmons, John M. Leong, Nufatt Buldo, Meghan Segal, Jeremy P. Jajosky, Audrey N. Rothberg, Paul G. Liesveld, Jane L. Oltvai, Zoltán N. Cold Spring Harb Mol Case Stud Research Report 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. Cold Spring Harbor Laboratory Press 2023-04 /pmc/articles/PMC10240839/ /pubmed/37160316 http://dx.doi.org/10.1101/mcs.a006241 Text en © 2023 El Hussein et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.
spellingShingle Research Report
El Hussein, Siba
Evans, Andrew G.
Fitzsimmons, John M.
Leong, Nufatt
Buldo, Meghan
Segal, Jeremy P.
Jajosky, Audrey N.
Rothberg, Paul G.
Liesveld, Jane L.
Oltvai, Zoltán N.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10240839/
https://www.ncbi.nlm.nih.gov/pubmed/37160316
http://dx.doi.org/10.1101/mcs.a006241
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