Laboratory of Lymphocyte Signaling and Oncoproteome

High TCL1 expression and intact T-cell receptor signaling define a hyperproliferative subset of T-cell prolymphocytic leukemia

Herling, M Patel, KA Teitell, MA Konopleva, M Ravandi, F Kobayashi, R Jones, D
Blood 111, 1January, 2008Pages: 328-37doi: 10.1182/blood-2007-07-101519

The T-cell leukemia 1 (TCL1) oncoprotein is overexpressed by chromosomal rearrangement in the majority of cases of T-cell prolymphocytic leukemia (T-PLL). In vitro, TCL1 can modulate the activity of the serine-threonine kinase AKT, a downstream effector of T-cell receptor (TCR) signaling. In a series of 86 T-PLL tumors, we show that expression of TCR, and levels of TCL1 and activated AKT are adverse prognostic markers. High-level TCL1 in TCR-expressing T-PLL is associated with higher presenting white blood cell counts, faster tumor cell doubling, and enhanced in vitro growth response to TCR engagement. In primary tumors and TCL1-transfected T-cell lines, TCR engagement leads to rapid recruitment of TCL1 and AKT to transient membrane activation complexes that include TCR-associated tyrosine kinases, including LCK. Pharmacologic inhibition of AKT activation alters the localization, stability, and levels of these transient TCL1-AKT complexes and reduces tumor cell growth. Experimental introduction and knockdown of TCL1 influence the kinetics and strength of TCR-mediated AKT activation. We propose that in T-PLL, TCL1 represents a highly regulated, targetable modulator of TCR-mediated AKT growth signaling.

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

November 21, 2019

New meta-analysis on JAK/STAT genomic alterations in T-PLL published in Cancers.

We congratulate Dr. Sebastian Oberbeck on his PhD defence!

We congratulate Dr. Sebastian Oberbeck on his PhD defence!

October 30, 2019

On October 30th, Sebastian Oberbeck successfully defended his PhD. Congratulations!

We congratulate Dr. Sabine Pützer on her PhD defence!

October 23, 2019

On October 23th, Sabine Pützer successfully defended her PhD. Congratulations!

Inter­national Symposium on T cells and T-cell lymphomas

Inter­national Symposium on T cells and T-cell lymphomas

August 20, 2019

The symposium hosted by the CONTROL-T consortium will take place from 20-21.09.2019 in Essen.