Hippo pathway-related genes expression is deregulated in myeloproliferative neoplasms

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Cacemiro, Maira da Costa ; Cominal, Jucara Gastaldi ; Pereira, Luiz Miguel ; Berzoti-Coelho, Maria Gabriela ; Berbel, Giovana Michelassi ; Baroni, Luciana ; Malta, Tathiane ; Tognon, Raquel ; Nunes, Natalia de Souza ; Souto, Elizabeth Xisto ; De Figueiredo-Pontes, Lorena Lobo ; Yatsuda, Ana Patricia ; de Castro, Fabiola Attie

• Document type: Journal article
• Source: MEDICAL ONCOLOGY; v. 39, n. 5, p. 11-pg., 2022-05-01.

Abstract

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. (AU)

• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/50947-7 - INCT 2014: in Stem Cell and Cell Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/23555-3 - Regulators microRNAs of HIPPO pathway in Chronic Myeloid Leukemia
• Grantee: Maria Gabriela Berzoti Coelho
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/19714-7 - Bone Marrow Mesenchymal Stromal Cells deregulation effect on BCR-ABL1-Myeloproliferative Neoplasms pathophysiology and progression
• Grantee: Fabíola Attié de Castro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/21866-1 - Cytokine-mediated regulation of normal and neoplastic hematopoietic stem cells by natural killer cells
• Grantee: Lorena Lôbo de Figueiredo Pontes
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 14/04234-9 - Expression of molecules of HIPPO/LATS pathway in chronic neoplasms myeloproliferative
• Grantee: Maira da Costa Cacemiro
• Support Opportunities: Scholarships in Brazil - Doctorate