The roles of SOX genes in AML are not entirely clear but emerging evidence, including that arising from studies in solid-cancers, showed that SOX genes can function as tumour suppressors or oncogenes and may be involved in key pathogenetic pathways in AML involving C/EBPα mutations, activation of β-catenin/Wnt and Hedgehog pathways and aberrant TP53 signals.
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.
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.
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.
We suggested that epigenetic modification of β-catenin and signal integration of CSLs, AP-2α, STATs, c-Jun and β-catenin could contribute to cell proliferation at AML and MDS.
While β-catenin has been demonstrated as an essential molecule and therapeutic target for various cancer stem cells (CSCs) including those driven by MLL fusions, here we show that transcriptional memory from cells of origin predicts AML patient survival and allows β-catenin-independent transformation in MLL-CSCs derived from hematopoietic stem cell (HSC)-enriched LSK population but not myeloid-granulocyte progenitors.
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>.
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.
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.
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.
The results provided unequivocal evidence for a novel tumor suppressor role of SOX7 in AML via a negative modulatory effect on the Wnt/β-catenin pathway.
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.