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 memorytype
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 TPLL
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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84401 |
| Date | 30 March 2023 |
| Creators | Braun, Till, Dechow, Annika, Friedrich, Gregor, Seifert, Michael, Stachelscheid, Johanna, Herling, Marco |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2234-943X, 775363 |
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