TCL1A Human

T-cell Leukemia/Lymphoma 1A (TCL1A) is an oncogene that plays a significant role in the development of various hematological malignancies. Discovered by Carlo Croce’s group in the 1980s, TCL1A has since been extensively studied for its involvement in lymphomagenesis and its potential as a therapeutic target .

The TCL1A gene encodes a protein known as TCL1, which is approximately 13 kDa in size. This protein functions by forming homodimers and acts as a co-activator of AKT kinases. AKT kinases are crucial for cell survival and proliferation, and TCL1 enhances their activity, thereby promoting cell growth and survival .

TCL1 is normally expressed in fetal tissues and early developmental stage lymphocytes. Its expression is tightly regulated during normal development. However, dysregulation of TCL1 expression can lead to various forms of leukemia and lymphoma. In particular, prolonged and increased expression of TCL1 in the late phases of thymocyte development can cause T-cell prolymphocytic leukemia (T-PLL) .

The dysregulation of TCL1 in T cells is often due to chromosomal translocations that bring the TCL1 gene under the control of T-cell receptor (TCR) enhancer elements. This leads to overexpression of TCL1, contributing to the development of T-PLL. In B cells, the mechanisms underlying TCL1 overexpression are less clear, as neither chromosomal translocations nor Epstein-Barr Virus (EBV) infection are typically involved .

TCL1 plays a central role in the development of various hematological malignancies, including chronic lymphocytic leukemia (B-CLL) and most lymphomas. Its expression has been observed in germinal center (GC) centroblasts, centrocytes, and post-GC memory B cells. Tumors arising from these cells, such as follicular lymphoma (FL), Burkitt lymphoma (BL), and diffuse large B cell lymphoma (DLBCL), often exhibit TCL1 expression .

TCL1 interacts with several key proteins, including ATM, HSP70, and TP63. These interactions enhance multiple signaling pathways, such as the PI3K and NF-κB pathways, which are crucial for cell survival and proliferation. Despite the lack of a well-defined enzymatic activity, TCL1’s role as a co-activator of AKT kinases and its interactions with other proteins make it a potential therapeutic target for TCL1-positive hematological malignancies .

Given its central role in lymphomagenesis and its involvement in multiple signaling pathways, TCL1 is considered a potential therapeutic target. Research is ongoing to develop therapies that can specifically target TCL1 and its interacting partners to treat TCL1-positive hematological malignancies .