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:	Till Braun, Annika Dechow, Gregor Friedrich, Michael Seifert, Johanna Stachelscheid, Marco Herling
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	T-PLL clonal evolution pathogenesis TCL1A ATM Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/49ba8721712f4235aa02df60ddb8df88
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id	oai:doaj.org-article:49ba8721712f4235aa02df60ddb8df88
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spelling	oai:doaj.org-article:49ba8721712f4235aa02df60ddb8df882021-11-19T05:06:31ZAdvanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact2234-943X10.3389/fonc.2021.775363https://doaj.org/article/49ba8721712f4235aa02df60ddb8df882021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.775363/fullhttps://doaj.org/toc/2234-943XT-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.Till BraunAnnika DechowGregor FriedrichMichael SeifertJohanna StachelscheidMarco HerlingMarco HerlingFrontiers Media S.A.articleT-PLLclonal evolutionpathogenesisTCL1AATMNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	T-PLL clonal evolution pathogenesis TCL1A ATM Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	T-PLL clonal evolution pathogenesis TCL1A ATM Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Till Braun Annika Dechow Gregor Friedrich Michael Seifert Johanna Stachelscheid Marco Herling Marco Herling Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact
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.
format	article
author	Till Braun Annika Dechow Gregor Friedrich Michael Seifert Johanna Stachelscheid Marco Herling Marco Herling
author_facet	Till Braun Annika Dechow Gregor Friedrich Michael Seifert Johanna Stachelscheid Marco Herling Marco Herling
author_sort	Till Braun
title	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_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_sort	advanced pathogenetic concepts in t-cell prolymphocytic leukemia and their translational impact
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/49ba8721712f4235aa02df60ddb8df88
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Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact

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