TCL1 expression patterns in Waldenström macroglobulinemia

Abstract

The oncogenic role of TCL1 in chronic lymphocytic leukemia is well established in transgenic mice. TCL1 expression in other B-cell malignancies has been also described: post-germinal center-derived malignancies, such as multiple myeloma, classically do not express TCL1. Waldenström macroglobulinemia is a post-germinal center malignancy that is known to be similar to chronic lymphocytic leukemia in terms of its gene expression profile. TCL1 expression has not been so far assessed in Waldenström macroglobulinemia. Transcriptomic explorations show that TCL1A expression is linked to signaling pathways and biological functions that are known to be involved in Waldenström macroglobulinemia as well as to gene signatures of interest in B-cell malignancies. We investigated TCL1 expression at the protein level in the bone marrow of a series of 59 patients with Waldenström macroglobulinemia: 76% of patients expressed TCL1, which appeared to be associated with a pejorative prognostic impact. TCL1 could have an oncogenic role in Waldenström macroglobulinemia, and deserves further exploration.

Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia

“…Specific lncRNAs influence gene expression programs, including the NF-κB signaling pathway 48 , interact with transcription factors 49 , and have been shown to be induced via the canonical TLR pathway involving MYD88 and NF-κB proteins 50 . Among TCL family members in this region, TCL1 has been shown to be aberrantly expressed in 73% of WM tumor samples 51 . Dysregulated TCL1 expression in B-cells enhances cell proliferation and survival, leading to cell transformation and mature B-cell tumors through multiple effector mechanisms, including NF-κB activation 52 – 55 .…”

Transgenic mouse model of IgM+ lymphoproliferative disease mimicking Waldenström macroglobulinemia

“…In vivo studies of this sort—under defined genetic, environmental and dietary conditions afforded by GEMMs of human cancer—may not only speed up the evaluation of new treatment options for patients with WM, 54, 55, 56, 57, 58 but also permit us to close thorny knowledge gaps in our understanding of the natural history of the disease. 59 New insights gleaned from integrated analyses of the WM genome 60 will guide future approaches to improve on the BCL2 + IL6 + AID − model.…”