Laboratory of Lymphocyte Signaling and Oncoproteome

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Alkylating deacetylase inhibitor tinostamustine in T-PLL

Advances and Perspectives in the Treatment of T-PLL

Abstract:

T cell prolymphocytic leukemia (T-PLL) is a rare mature T cell tumor. Available treatment options in this aggressive disease are largely inefficient and patient outcomes are highly dissatisfactory. Current therapeutic strategies mainly employ the CD52-antibody alemtuzumab as the most active single agent. However, sustained remissions after sole alemtuzumab-based induction are exceptions. Responses after available second-line strategies are even less durable. More profound disease control or rare curative outcomes can currently only be expected after a consolidating allogeneic hematopoietic stem cell transplantation (allo-HSCT) in best first response. However, only 30-50% of patients are eligible for this procedure. Major advances in the molecular characterization of T-PLL during recent years have stimulated translational studies on potential vulnerabilities of the T-PLL cell. We summarize here the current state of “classical” treatments and critically appraise novel (pre)clinical strategies.

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Advances and Perspectives in the Treatment of T-PLL

Published under a Creative Commons Attribution 4.0 International License

Postet on February 25, 2020

JAK/STAT-Activating Genomic Alterations Are a Hallmark of T-PLL

Missense mutations of JAK and STAT genes are frequently found in T-PLL. However, sequencing analyses of the JAK/STAT pathway have been performed in small cohorts, due to the limited number of patient samples. Here we conducted a meta-analysis that re-evaluated the genomic landscape of the JAK/STAT pathway and its regulators in 275 T-PLL cases. Interestingly, next to gain of function mutations in JAK and STAT genes, a significant proportion of genes encoding for potential negative regulators of STAT5B showed genomic losses. Overall, considering such losses of negative regulators and the GOF mutations in JAK and STAT genes, we found that a total of 89.8% of T-PLL revealed a genomic aberration potentially explaining enhanced STAT5B activity.

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JAK/STAT-Activating Genomic Alterations Are a Hallmark of T-PLL

Postet on November 21, 2019

We congratulate Dr. Sebastian Oberbeck on his PhD defence!

On October 30th, Sebastian Oberbeck successfully defended his PhD. The title of his thesis: “The T-cell receptor and it’s signaling in T-cell Prolymphocytic Leukemia”. Congratulations!

Postet on October 30, 2019
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