Journal Article

DKFZ-2024-00908

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png T-bet suppresses proliferation of malignant B cells in chronic lymphocytic leukemia.

Rössner, P. (First author)DKFZ* ; Seufert, I. ; Chapaprieta, V. ; Jayabalan, R.DKFZ* ; Briesch, H.DKFZ* ; Massoni-Badosa, R.DKFZ* ; Boskovic, P.DKFZ* ; Beckendorff, J. ; Roider, T. ; Arseni, L.DKFZ* ; Coelho, M.DKFZ* ; Chakraborty, S. ; Vaca, A. ; Sivina, M. ; Muckenhuber, M.DKFZ* ; Rodriguez-Rodriguez, S. ; Bonato, A. ; Herbst, S. A. ; Zapatka, M.DKFZ* ; Sun, C. ; Kretzmer, H. ; Naake, T. ; Bruch, P.-M. ; Czernilofsky, F. ; Ten Hacken, E. ; Schneider, M.DKFZ* ; Helm, D.DKFZ* ; Yosifov, D.DKFZ* ; Kauer, J. ; Danilov, A. V. ; Bewarder, M. ; Heyne, K. ; Schneider, C. ; Stilgenbauer, S. ; Wiestner, A. ; Mallm, J.-P.DKFZ* ; Burger, J. A. ; Efremov, D. G. ; Lichter, P.DKFZ* ; Dietrich, S. ; Martín-Subero, J. I. ; Rippe, K.DKFZ* ; Seiffert, M. (Last author)DKFZ*

2024
American Society of Hematology Washington, DC

This record in other databases:  

Please use a persistent id in citations: doi:10.1182/blood.2023021990

Abstract: The T-box transcription factor T-bet is known as a master regulator of T-cell response but its role in malignant B cells is not sufficiently explored. Here, we conducted single-cell resolved multi-omics analyses of malignant B cells from patients with chronic lymphocytic leukemia (CLL) and studied a CLL mouse model with genetic knockout of TBX21. We found that T-bet acts as a tumor suppressor in malignant B cells by decreasing their proliferation rate. NF-κB activity induced by inflammatory signals provided by the microenvironment, triggered T-bet expression which impacted on promoter proximal and distal chromatin co-accessibility and controlled a specific gene signature by mainly suppressing transcription. Gene set enrichment analysis identified a positive regulation of interferon signaling, and a negative control of proliferation by T-bet. In line, we showed that T-bet represses cell cycling and is associated with longer overall survival of CLL patients. Our study uncovers a novel tumor suppressive role of T-bet in malignant B cells via its regulation of inflammatory processes and cell cycling which has implications for stratification and therapy of CLL patients. Linking T-bet activity to inflammation explains the good prognostic role of genetic alterations in inflammatory signaling pathways in CLL.

Note: #EA:B060#LA:B060# / 2024 Aug 1;144(5):510-524

---

Contributing Institute(s):

1. B060 Molekulare Genetik (B060)
2. B066 Chromatin-Netzwerke (B066)
3. Proteomics (W120)
4. B061 Mechanismen d. Leukämogenese (B061)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 20 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---