Hippo pathway-related genes expression is deregulated in myeloproliferative neoplasms.
Maira da Costa CacemiroJuçara Gastaldi CominalLuiz Miguel PereiraMaria Gabriela Berzoti-CoelhoGiovana Michelassi BerbelLuciana BaroniTathiane MaltaRaquel TognonNatalia de Souza NunesElizabeth Xisto SoutoLorena Lobo de Figueiredo-PontesAna Patricia YatsudaFabíola Attié de CastroPublished in: Medical oncology (Northwood, London, England) (2022)
Myeloproliferative neoplasms (MPN) are hematological disorders characterized by increased proliferation of precursor and mature myeloid cells. MPN patients may present driver mutations in JAK2, MPL, and CALR genes, which are essential to describe the molecular mechanisms of MPN pathogenesis. Despite all the new knowledge on MPN pathogenesis, many questions remain to be answered to develop effective therapies to cure MPN or impair its progression to acute myeloid leukemia. The present study examined the expression levels of the Hippo signaling pathway members in patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), as well as the role that they play in disease pathogenesis. The Hippo pathway is a tumor suppressor pathway that participates in the regulation of cell proliferation, differentiation, and death. Our main finding was that the expression of tumor suppressor genes from Hippo pathway were downregulated and seemed to be associated with cell resistance to apoptosis and increased proliferation rate. Therefore, the decreased expression of Hippo pathway-related genes may contribute to the malignant phenotype, apoptosis resistance, and cell proliferation in MPN pathogenesis.
Keyphrases
- poor prognosis
- signaling pathway
- cell proliferation
- cell cycle arrest
- acute myeloid leukemia
- pi k akt
- induced apoptosis
- oxidative stress
- endoplasmic reticulum stress
- binding protein
- healthcare
- cell death
- stem cells
- ejection fraction
- bone marrow
- prognostic factors
- acute lymphoblastic leukemia
- patient reported outcomes
- patient reported