Exploring the Molecular Landscape of Myelofibrosis, with a Focus on Ras and Mitogen-Activated Protein (MAP) Kinase Signaling.
Exploring the Molecular Landscape of Myelofibrosis, with a Focus on Ras and Mitogen-Activated Protein (MAP) Kinase Signaling.
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DOI：
10.3390/cancers15184654
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发表时间：
2023-09-21
期刊：
影响因子：
5.2
通讯作者：
Li, Qing
中科院分区：
文献类型：
--
作者：
Reynolds, Samuel B.;Pettit, Kristen;Kandarpa, Malathi;Talpaz, Moshe;Li, Qing
骨髓纤维化是一种由干细胞突变驱动的骨髓疾病，导致红细胞、白细胞以及血小板的骨髓生成进行性失败。随着时间的推移，患者还可能患上白血病（一种白细胞癌症）。虽然唯一的治疗方法是骨髓移植，但许多患者不适合接受治疗，需要针对症状性疾病进行治疗。最常见的疗法针对一种称为“Jak”的蛋白质，但对这些药物的耐药性很常见，因此探索这种耐药性如何表现的替代机制至关重要。除了 Jak 之外，骨髓纤维化中另一个新兴但尚未充分探索的靶点是一组称为“Ras/MAP 激酶”的蛋白质。本综述的目的是介绍 Ras/MAP 激酶信号传导及其在骨髓纤维化中的作用的研究，我们希望这些研究将扩大提供者如何看待和针对这种疾病，最终改善患者的生活。骨髓纤维化（MF）是一种克隆性骨髓增生性肿瘤（MPN），其临床特征为髓外造血引起的血细胞减少、疲劳和脾肿大。 MF 通常由 JAK2、MPL 和 CALR 突变引起，表现为 Jak/Stat 信号传导过度活跃。三阴性 MF 在不存在 JAK2、MPL 和 CALR 的情况下诊断，但当满足临床、形态学标准并且存在其他突变（包括 ASXL1、EZH2 和 SRSF2）时。虽然 MF 的临床和经典分子特征已得到充分证实，但新出现的证据表明，存在其他突变，特别是 Ras/MAP 激酶信号通路内的突变，并且可能在疾病发病机制和治疗反应中发挥重要作用。据报道，仅 KRAS 和 NRAS 突变分别存在于高达 15% 和 14% 的 MF 患者中，而预计激活 Ras 信号传导的其他突变，如 CBL、NF1、BRAF 和 PTPN11，总共存在于多达 21% 的患者中。对 MF 中 RAS 和相关通路突变的患病率及其发病机制的研究对于更好地了解这种疾病并最终确定新的治疗靶点至关重要。
Myelofibrosis is a disease arising from bone marrow driven by mutations in stem cells, which results in progressive failure of marrow production in red and white blood cells as well as platelets. Patients can also develop leukemia (a cancer of white blood cells) over time. While the only cure is a bone marrow transplant, many patients are not candidates and require treatment for symptomatic disease. The most common therapies target a protein known as “Jak” but resistance to these agents is common, making the exploration of alternative mechanisms for how such resistance manifests essential. Beyond Jak, another emerging yet under-explored target in myelofibrosis is a group of proteins known as “Ras/MAP Kinase”. The aim of this review is to present research into Ras/MAP Kinase signaling and its role in myelofibrosis, which we hope will expand how providers view and target this disease, ultimately improving the lives of patients. Myelofibrosis (MF) is a clonal myeloproliferative neoplasm (MPN) characterized clinically by cytopenias, fatigue, and splenomegaly stemming from extramedullary hematopoiesis. MF commonly arises from mutations in JAK2, MPL, and CALR, which manifests as hyperactive Jak/Stat signaling. Triple-negative MF is diagnosed in the absence of JAK2, MPL, and CALR but when clinical, morphologic criteria are met and other mutation(s) is/are present, including ASXL1, EZH2, and SRSF2. While the clinical and classic molecular features of MF are well-established, emerging evidence indicates that additional mutations, specifically within the Ras/MAP Kinase signaling pathway, are present and may play important role in disease pathogenesis and treatment response. KRAS and NRAS mutations alone are reportedly present in up to 15 and 14% of patients with MF (respectively), and other mutations predicted to activate Ras signaling, such as CBL, NF1, BRAF, and PTPN11, collectively exist in as much as 21% of patients. Investigations into the prevalence of RAS and related pathway mutations in MF and the mechanisms by which they contribute to its pathogenesis are critical in better understanding this condition and ultimately in the identification of novel therapeutic targets.
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影响因子：
3.5
作者：
Maddali M;Kulkarni UP;Ravindra N;Jajodia E;Arunachalam AK;Suresh H;Venkatraman A;George B;Mathews V;Balasubramanian P
通讯作者：
Balasubramanian P
影响因子：
16.6
作者：
Ross BD;Jang Y;Welton A;Bonham CA;Palagama DSW;Heist K;Boppisetti J;Imaduwage KP;Robison T;King LR;Zhang EZ;Amirfazli C;Luker KE;Lee WY;Luker GD;Chenevert TL;Van Dort ME
通讯作者：
Van Dort ME
影响因子：
4.4
作者：
Hussain, Muhammad Ramzan Manwar;Baig, Mukhtiar;Mohamoud, Hussein Sheik Ali;Ul-Haq, Zaheer;Hoessli, Daniel C.;Khogeer, Ghaidaa Siraj;Al-Sayed, Ranem Radwan;Al-Aama, Jumana Yousuf
通讯作者：
Al-Aama, Jumana Yousuf
影响因子：
5.4
作者：
Aubrey, Brandon J.;Strasser, Andreas;Kelly, Gemma L.
通讯作者：
Kelly, Gemma L.
DOI：
10.1016/bs.acr.2021.07.002
发表时间：
2022-01-01
期刊：
RAS
影响因子：
--
作者：
Chou, Yu-Ting;Bivona, Trever G.
通讯作者：
Bivona, Trever G.