Tcl1, short for T-cell leukemia/lymphoma 1, is a proto-oncogene. It functions as a co-activator of the serine/threonine AKT/PKB kinase, enhancing its activity, and is involved in pathways related to cell proliferation, survival, and energy metabolism [3,4]. Tcl1 is also expressed in totipotent cells of mouse pre-implantation embryos and is among the genes required for maintaining the mitotic self-renewal state of embryonic stem cells, highlighting its importance in early development [1]. Genetic models, such as mouse models, are valuable for studying Tcl1.

In the Eµ-Tcl1 mouse model, a B-cell specific overexpression of human Tcl1 leads to a CLL-like disease with increasing age. This model has been crucial for developing targeted therapies against constitutive B-cell receptor signaling in CLL, though its translatability to human CLL is debated as it lacks the driver mutations found in patients [2]. In T-cell prolymphocytic leukemia (T-PLL), Tcl1 overexpression is a common driver of pathogenesis, and the cooperativity between Tcl1 family members and ATM seems unique to T-PLL among T-cell neoplasms [5].

In conclusion, Tcl1 plays essential roles in cell proliferation, survival, and energy metabolism, and is crucial in early development. Mouse models, like the Eµ-Tcl1 mouse, have significantly contributed to understanding its role in CLL. Tcl1 overexpression is also a key factor in T-PLL pathogenesis, highlighting its importance in lymphoid malignancies.

References:

1. Fiorenza, Maria Teresa, Rava, Alessandro. 2019. The TCL1 function revisited focusing on metabolic requirements of stemness. In Cell cycle (Georgetown, Tex.), 18, 3055-3063. doi:10.1080/15384101.2019.1672465. https://pubmed.ncbi.nlm.nih.gov/31564197/

2. Floerchinger, Alessia, Seiffert, Martina. 2024. Lessons learned from the Eµ-TCL1 mouse model of CLL. In Seminars in hematology, 61, 194-200. doi:10.1053/j.seminhematol.2024.05.002. https://pubmed.ncbi.nlm.nih.gov/38839457/

3. Noguchi, Masayuki, Ropars, Virginie, Roumestand, Christian, Suizu, Futoshi. 2007. Proto-oncogene TCL1: more than just a coactivator for Akt. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 21, 2273-84. doi:. https://pubmed.ncbi.nlm.nih.gov/17360849/

4. Teitell, Michael A. . The TCL1 family of oncoproteins: co-activators of transformation. In Nature reviews. Cancer, 5, 640-8. doi:. https://pubmed.ncbi.nlm.nih.gov/16056259/

5. Gutierrez, Marc, Bladek, Patrick, Goksu, Busra, Bixby, Dale, Wilcox, Ryan. 2023. T-Cell Prolymphocytic Leukemia: Diagnosis, Pathogenesis, and Treatment. In International journal of molecular sciences, 24, . doi:10.3390/ijms241512106. https://pubmed.ncbi.nlm.nih.gov/37569479/