Revisiting β‐Catenin Signaling in T‐Cell Development and T‐Cell Acute Lymphoblastic Leukemia

Abstract

Catenin/CTNNB1 is critical for leukemia initiation or the stem cell capacity of several hematological malignancies. This review focuses on a general evaluation of -catenin function in normal T-cell development and T-cell acute lymphoblastic leukemia (T-ALL). The integration of the existing literature offers a state-of-the-art dissection of the complexity of -catenin function in leukemia initiation and maintenance in both Notch-dependent and independent contexts. In addition, -catenin mutations are screened for in T-ALL primary samples, and it is found that they are rare and with little clinical relevance. Transcriptional analysis of Wnt family members (Ctnnb1, Axin2, Tcf7, and Lef1) and Myc in different publicly available T-ALL cohorts indicates that the expression of these genes may correlate with T-ALL subtypes and/or therapy outcomes.

FZD6 triggers Wnt–signalling driven by WNT10BIVS1 expression and highlights new targets in T‐cell acute lymphoblastic leukemia

“…Our recent findings also highlight the high prevalence of a WNT10B rearrangement ( WNT10B R ), involving intron 1 proximal to the exon 2, and expressing the WNT10B IVS1 transcript in acute myeloid leukemia with normal karyotype 27 . Based on prior results, it has been suggested the importance of abnormal Wnt activation in T‐ALL patients, supported by patients being characterized by a minor subpopulation of Wnt‐active cells highly enriched for leukemia‐initiating cells (LICs) with both T‐ and myeloid cell potential 16,26,31,46 . The role played by the Wnt signaling in T‐ALL pathogenesis is overly complex and the precise mechanisms underlying leukemia development remain to be elucidated.…”

“… 27 Based on prior results, it has been suggested the importance of abnormal Wnt activation in T‐ALL patients, supported by patients being characterized by a minor subpopulation of Wnt‐active cells highly enriched for leukemia‐initiating cells (LICs) with both T‐ and myeloid cell potential. 16 , 26 , 31 , 46 The role played by the Wnt signaling in T‐ALL pathogenesis is overly complex and the precise mechanisms underlying leukemia development remain to be elucidated. Paralleling our own observations in an Italian multicentric cohort of newly diagnosed T‐ALL patients, we detected a high frequency of WNT10B IVS1 expression in bone marrow samples at diagnosis.…”

The Role of β-Catenin in Th1 Immune Response against Tuberculosis and Profiles of Expression in Patients with Pulmonary Tuberculosis

“…β -Catenin has been thought to be involved in the regulation of cell fate, such as proliferation, differentiation, and apoptosis or T cell development [ 16 , 17 ]. In most published studies, β -catenin has a close association with the pathogenesis of malignant diseases and is a therapeutic target for cancer in view of its function to promote tumor cell proliferation [ 18 ].…”

Phosphorylation-Dependent Regulation of WNT/Beta-Catenin Signaling

“…However, β-catenin is not mutated in pediatric T-ALL, and even if it is found to be mutated in any T-ALL cell line or patient sample, this holds no clinical significance ( 54 ). The most common activating missense mutation found in the endometroid carcinoma subtype of epithelial ovarian cancer (EOC) is in the β-catenin gene, CTNNB1 , accounting for 54% of cases ( 55 ).…”