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Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact

T-cell prolymphocytic leukemia (T-PLL) is the most common mature T-cell leukemia. It is a typically aggressively growing and chemotherapy-resistant malignancy with a poor prognosis. T-PLL cells resemble activated, post-thymic T-lymphocytes with memory-type effector functions. Constitutive transcript...

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Autores principales: Braun, Till, Dechow, Annika, Friedrich, Gregor, Seifert, Michael, Stachelscheid, Johanna, Herling, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639578/
https://www.ncbi.nlm.nih.gov/pubmed/34869023
http://dx.doi.org/10.3389/fonc.2021.775363
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author Braun, Till
Dechow, Annika
Friedrich, Gregor
Seifert, Michael
Stachelscheid, Johanna
Herling, Marco
author_facet Braun, Till
Dechow, Annika
Friedrich, Gregor
Seifert, Michael
Stachelscheid, Johanna
Herling, Marco
author_sort Braun, Till
collection PubMed
description T-cell prolymphocytic leukemia (T-PLL) is the most common mature T-cell leukemia. It is a typically aggressively growing and chemotherapy-resistant malignancy with a poor prognosis. T-PLL cells resemble activated, post-thymic T-lymphocytes with memory-type effector functions. Constitutive transcriptional activation of genes of the T-cell leukemia 1 (TCL1) family based on genomic inversions/translocations is recognized as a key event in T-PLL’s pathogenesis. TCL1’s multiple effector pathways include the enhancement of T-cell receptor (TCR) signals. New molecular dependencies around responses to DNA damage, including repair and apoptosis regulation, as well as alterations of cytokine and non-TCR activation signaling were identified as perturbed hallmark pathways within the past years. We currently witness these vulnerabilities to be interrogated in first pre-clinical concepts and initial clinical testing in relapsed/refractory T-PLL patients. We summarize here the current knowledge on the molecular understanding of T-PLL’s pathobiology and critically assess the true translational progress around this to help appraisal by caregivers and patients. Overall, the contemporary concepts on T-PLL’s pathobiology are condensed in a comprehensive mechanistic disease model and promising interventional strategies derived from it are highlighted.
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spelling pubmed-86395782021-12-04 Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact Braun, Till Dechow, Annika Friedrich, Gregor Seifert, Michael Stachelscheid, Johanna Herling, Marco Front Oncol Oncology T-cell prolymphocytic leukemia (T-PLL) is the most common mature T-cell leukemia. It is a typically aggressively growing and chemotherapy-resistant malignancy with a poor prognosis. T-PLL cells resemble activated, post-thymic T-lymphocytes with memory-type effector functions. Constitutive transcriptional activation of genes of the T-cell leukemia 1 (TCL1) family based on genomic inversions/translocations is recognized as a key event in T-PLL’s pathogenesis. TCL1’s multiple effector pathways include the enhancement of T-cell receptor (TCR) signals. New molecular dependencies around responses to DNA damage, including repair and apoptosis regulation, as well as alterations of cytokine and non-TCR activation signaling were identified as perturbed hallmark pathways within the past years. We currently witness these vulnerabilities to be interrogated in first pre-clinical concepts and initial clinical testing in relapsed/refractory T-PLL patients. We summarize here the current knowledge on the molecular understanding of T-PLL’s pathobiology and critically assess the true translational progress around this to help appraisal by caregivers and patients. Overall, the contemporary concepts on T-PLL’s pathobiology are condensed in a comprehensive mechanistic disease model and promising interventional strategies derived from it are highlighted. Frontiers Media S.A. 2021-11-19 /pmc/articles/PMC8639578/ /pubmed/34869023 http://dx.doi.org/10.3389/fonc.2021.775363 Text en Copyright © 2021 Braun, Dechow, Friedrich, Seifert, Stachelscheid and Herling https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Braun, Till
Dechow, Annika
Friedrich, Gregor
Seifert, Michael
Stachelscheid, Johanna
Herling, Marco
Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact
title Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact
title_full Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact
title_fullStr Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact
title_full_unstemmed Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact
title_short Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact
title_sort advanced pathogenetic concepts in t-cell prolymphocytic leukemia and their translational impact
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639578/
https://www.ncbi.nlm.nih.gov/pubmed/34869023
http://dx.doi.org/10.3389/fonc.2021.775363
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