Laboratory of Lymphocyte Signaling and Oncoproteome

All news

New article accepted for publication

Our latest article “Non-canonical effector functions of the T-memory-like T-PLL cell are shaped by cooperative TCL1A and TCR signaling” by Sebastian Oberbeck, Alexandra Schrader, Kathrin Warner et al. has been accepted for publication in Blood.

In this study, we report two major findings:

  • T-PLL cells resemble activated T-lymphocytes with augmented memory-type effector functions including a marked anergy to apoptotic triggers
  • specific co-opting loss of inhibitory receptors and the overexpressed signal enhancer TCL1A lower thresholds towards permissive TCR input

We will add a link to the article as soon as the publication process has been completed.

Postet on August 30, 2020

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.

Read the full article:

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.

Read the paper:

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

Postet on November 21, 2019
Show more news →