The Role of β-Catenin in Bcr/Abl Negative Myeloproliferative Neoplasms: An Immunohistochemical Study

Canonical Wnt/β-Catenin Signaling Pathway Is Dysregulated in Patients With Primary and Secondary Myelofibrosis

“…This effect can be attenuated by silencing beta-TrCP with specific shRNA, identifying beta-TrCP as cross-talk gene between JAK/STAT and Wnt/β-catenin signaling pathways. Expression of β-catenin in our study shows no association with either JAK2 V617F mutational status or JAK2 V617F allele burden which is in line with previous observations regarding Ph-MPNs 15,22 suggesting that β-catenin expression could independently contribute to pathogenesis of Ph-MPNs but future studies are needed.…”

“…Second study was done by Jauregui et al 14 who used immunohistochemistry to demonstrate lower expression of β-catenin in megakaryocytes of PMF and CML patients in comparison to PRV and ET. Third study was done by Geduk et al 15 who used immunohistochemistry to analyze β-catenin expression in Ph-MPN subsets distinguishing expression in myeloid cells, megakaryocytes and vascular endothelial cells. They showed lower expression of β-catenin in megakaryocytes of PMF patients in comparison to ET and PRV (there was no difference between PMF and control group), no difference in β-catenin expression in myeloid cells among tested subsets and higher β-catenin expression in vascular endothelial cells of PMF patients in comparison to PRV, ET and control group.…”

“…9 Aberrant activation of canonical Wnt/β-catenin signaling increases propensity for cell malignant transformation and has been implicated in a wide array of malignant hematological disorders like multiple myeloma 10 , chronic lymphocytic leukemia 11 , chronic myelogenous leukemia (CML) 12 , acute myeloid leukaemia 13 etc. There are few reports suggesting its dysregulation in PhMPNs 14,15 with PMF patients receiving only limited attention.…”

Wnt/beta-catenin pathway: modulating anticancer immune response

“…In addition, MCL-ILs were shown to be sensitive when targeted downstream at β-catenin-mediated transcription complex with inhibitors such as CCT036477, iCRT14, and PKF118-310. β-catenin mRNA or protein expression was shown to be upregulated in the bone marrow aspirates of patients with myelofibrosis and in other Philadelphia-negative myeloproliferative neoplasms [52, 53]. The Wnt/β-catenin pathway is also involved in the pathogenesis of multiple myeloma (MM), with silencing of the pathway resulting in autophagy and apoptosis in MM cells [54].…”

Higher Sclerostin/SOST expression is associated with lower percentage of circulatory blasts and better prognosis in patients with myelofibrosis

“…It is produced by osteocytes and bone marrow (BM) cells. cWNT activation is implicated in pathogenesis of Philadelphia chromosome negative myeloproliferative neoplasms (Ph-MPNs) [2,3], diseases characterized by remodelling of BM stroma and development of BM fibrosis/osteosclerosis during course of the disease. We aimed to investigate Sclerostin/SOST expression in BM tissues of patients with primary (PMF) and secondary post Ph-MPN myelofibrosis (SMF) and to assess its clinical correlations.…”