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Hippo 通路相关基因表达在骨髓增殖性肿瘤中失调。

Hippo pathway-related genes expression is deregulated in myeloproliferative neoplasms.

机构信息

Laboratório de Fisiopatologia das Doenças Hematológicas, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo - USP, Av. do Café, s/nº. Campus Universitário, Ribeirão Preto, SP, 14040-903, Brazil.

Department of Pharmacy, Federal University of Juiz de Fora, Campus Governador Valadares, Governador Valadares, MG, Brazil.

出版信息

Med Oncol. 2022 May 23;39(5):97. doi: 10.1007/s12032-022-01696-x.

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.

摘要

骨髓增殖性肿瘤(MPN)是一种血液系统疾病,其特征为前体细胞和成熟髓系细胞的增殖增加。MPN 患者可能存在 JAK2、MPL 和 CALR 基因的驱动突变,这些突变对于描述 MPN 发病机制的分子机制至关重要。尽管对 MPN 发病机制有了很多新的认识,但仍有许多问题有待回答,以开发有效的治疗方法来治愈 MPN 或阻止其进展为急性髓系白血病。本研究检测了 Hippo 信号通路成员在真性红细胞增多症(PV)、原发性血小板增多症(ET)和原发性骨髓纤维化(PMF)患者中的表达水平,以及它们在疾病发病机制中的作用。Hippo 通路是一种肿瘤抑制通路,参与细胞增殖、分化和死亡的调节。我们的主要发现是 Hippo 通路中的肿瘤抑制基因表达下调,似乎与细胞对凋亡的抵抗和增殖率增加有关。因此,Hippo 通路相关基因的表达下调可能导致 MPN 发病机制中的恶性表型、凋亡抵抗和细胞增殖。

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