Altogether, these results show that despite a frequent β-catenin upregulation in AML, leukemia-initiating cells might not be 'addicted' to this pathway and thus targeted therapy against β-catenin might not be successful in all patients.
Besides haematopoiesis, beta-catenin prominently marked bone marrow vascularity and diverse stroma cells. beta-Catenin gene was inversely expressed in AML and ALL with a lack of protein expression in neoplastic cells in ALL.
Differential antigen expression and aberrant signaling via PI3/AKT, MAP/ERK, JAK/STAT, and Wnt/β catenin pathways in Lin-/CD38-/CD34+ cells in acute myeloid leukemia.
Here we show that an activating mutation of β-catenin in mouse osteoblasts alters the differentiation potential of myeloid and lymphoid progenitors leading to development of acute myeloid leukaemia with common chromosomal aberrations and cell autonomous progression.
Importantly, β-catenin inhibition abrogated the microenvironmental protection afforded the leukemic stem/progenitor cells.<b>Conclusions:</b> Disrupting Wnt/β-catenin signaling exerts potent activities against AML stem/progenitor cells and synergizes with FLT3 inhibition in <i>FLT3</i>-mutant AML.
In conclusion, miR-34b suppressed AML cell proliferation and survival by targeting HSF1, in turn leading to the inactivation of Wnt-β-catenin pathway, which may highlight a new therapeutic approach for AML.
In our cohort, beta-catenin expression was correlated with the clonogenic proliferation of AML-colony forming cells (AML-CFC or CFU-L) in methylcellulose in the presence of 5637-conditioned medium, and more strikingly with self-renewing of leukemic cells, as assessed in vitro by a re-plating assay.
Inhibition of β-catenin also stunted growth and colony-forming abilities of primary bone marrow cells from del(5q) AML patients <i>in vitro</i> Overall, our data support the idea that β-catenin could serve as a therapeutic target for the treatment of myeloid neoplasms with del(5q).<i></i>.
Knocking down CTNNB1 or NR4A1 in AML-MSC-co-cultured-CD34<sup>+</sup> cells increased leukaemia-reactive T-effector cells production and rescued anti-leukaemia immunity.
Nuclear localization of non-phosphorylated, active beta-catenin is a measure of Wnt pathway activation and is associated with adverse outcome in patients with acute myeloid leukemia (AML).
Resected hepatic AMLs (n = 16) were reviewed; reticulin stain, immunohistochemistry for glutamine synthetase (GS), β-catenin and liver fatty acid binding protein (LFABP) were performed along with Sanger sequencing of exon 3 of CTNNB1 and next-generation sequencing (NGS).
SALL1 inhibition resulted in decreased cellular proliferation and in inferior AML engraftment in NSG mice and it was also associated with upregulation of PTEN and downregulation of m-TOR, β-catenin, and NF-қB expression.
SOX12 may be involved in leukaemia progression by regulating the expression of β-catenin and then interfering with TCF/Wnt pathway, which may be a target for AML.
Targeting FAK or β-catenin efficiently eradicates primitive leukemic cells in vitro suggesting that FAK could be a useful therapeutic target for improved treatment of poor prognosis AML cases.