Wnt Signaling in Hematological Malignancies.
Wnt Signaling in Hematological Malignancies.
复制标题
DOI：
10.1016/bs.pmbts.2017.11.002
复制
发表时间：
2018-01
影响因子：
--
通讯作者：
Willert K
中科院分区：
文献类型：
--
作者：
Grainger S;Traver D;Willert K
白血病和淋巴瘤是一个广泛涵盖的术语，用于各种血液恶性肿瘤，其影响所有年龄的人，并且在美国每年导致大约23，000例死亡（Siegel RL，米勒KD，Jemal A.癌症统计，2016年。CA Cancer J Clin.2016;66（1）：7-30）。造血干细胞（HSC）是位于层级顶端的组织特异性干细胞，其通过逐渐受限的祖细胞群体产生所有终末分化的血细胞，这是已知为Wnt响应性的过程。特别是，祖细胞群体在致癌过程中会发生不受控制的扩张，即常见的骨髓祖细胞和常见的淋巴祖细胞，以及成髓细胞和成淋巴细胞。这些细胞类型的不受调节的生长主要导致三种类型的血癌（即，白血病、淋巴瘤和骨髓瘤），其经常表现出Wnt信号通路的失调。通常，白血病是由骨髓祖细胞的扩增引起的，导致白色血细胞的过度产生;因此，患者不能产生足够数量的红细胞和血小板。同样，淋巴细胞的过度产生导致淋巴系统的堵塞和淋巴瘤中免疫系统的损害。最后，血液中浆细胞的癌症被称为骨髓瘤，这也会导致免疫系统衰竭。在这三种类型的血癌中，每一种都有多种亚型，通常以其发病的时间轴和起源的细胞类型为特征。其中，85%的白血病包括在四种最常见的疾病中，即急性髓性白血病（AML）、慢性髓性白血病（CML）、急性淋巴细胞白血病（ALL）和慢性淋巴细胞白血病（CLL）; AML占白血病相关死亡的大多数（Siegel RL，米勒KD，Jemal A.癌症统计，2016年。CA Cancer J Clin.2016;66（1）：7-30）。通过了解HSC如何正常发育和维持，我们可以了解这些途径的正常功能在血癌进展期间是如何被破坏的; Wnt途径在正常和恶性造血的调节中都很重要。在本章中，我们将讨论Wnt信号在正常和异常造血中的作用。我们对Wnt和HSC之间关系的理解将为治疗靶点提供新的见解。
Leukemia and lymphoma are a wide encompassing term for a diverse set of blood malignancies that affect people of all ages and result in approximately 23,000 deaths in the United States per year (Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.). Hematopoietic stem cells (HSCs) are tissue-specific stem cells at the apex of the hierarchy that gives rise to all of the terminally differentiated blood cells, through progressively restricted progenitor populations, a process that is known to be Wnt-responsive. In particular, the progenitor populations are subject to uncontrolled expansion during oncogenic processes, namely the common myeloid progenitor and common lymphoid progenitor, as well as the myeloblast and lymphoblast. Unregulated growth of these cell-types leads to mainly three types of blood cancers (i.e., leukemia, lymphoma, and myeloma), which frequently exhibit deregulation of the Wnt signaling pathway. Generally, leukemia is caused by the expansion of myeloid progenitors, leading to an overproduction of white blood cells; as such, patients are unable to make sufficient numbers of red blood cells and platelets. Likewise, an overproduction of lymphocytes leads to clogging of the lymph system and impairment of the immune system in lymphomas. Finally, cancer of the plasma cells in the blood is called myeloma, which also leads to immune system failure. Within each of these three types of blood cancers, there are multiple subtypes, usually characterized by their timeline of onset and their cell type of origin. Of these, 85% of leukemias are encompassed by the four most common diseases, that is, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL); AML accounts for the majority of leukemia-related deaths (Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.). Through understanding how HSCs are normally developed and maintained, we can understand how the normal functions of these pathways are disrupted during blood cancer progression; the Wnt pathway is important in regulation of both normal and malignant hematopoiesis. In this chapter, we will discuss the role of Wnt signaling in normal and aberrant hematopoiesis. Our understanding the relationship between Wnt and HSCs will provide novel insights into therapeutic targets.
登录
查看更多内容
影响因子：
11.4
作者：
BODRUG, SE;WARNER, BJ;ADAMS, JM
通讯作者：
ADAMS, JM
DOI：
10.1073/pnas.0305855101
发表时间：
2004-04-20
影响因子：
11.1
作者：
Derksen, PWB;Tjin, E;Pals, ST
通讯作者：
Pals, ST
DOI：
10.1073/pnas.0712148105
发表时间：
2008-02-26
影响因子：
11.1
作者：
Fukuda, Tetsuya;Chen, Liguang;Kipps, Thomas J.
通讯作者：
Kipps, Thomas J.
影响因子：
2.7
作者：
Dharmapuri, Gangappa;Doneti, Ravinder;Kalle, Arunasree M.
通讯作者：
Kalle, Arunasree M.
影响因子：
64.8
作者：
通讯作者：
--