Tsapogas Panagiotis, Mooney Ciaran James, Brown Geoffrey, Rolink Antonius
Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Mattenstrasse 28, Basel 4058, Switzerland.
Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Edbgaston, Birmingham B15 2TT, UK.
Int J Mol Sci. 2017 May 24;18(6):1115. doi: 10.3390/ijms18061115.
The cytokine Fms-like tyrosine kinase 3 ligand (FL) is an important regulator of hematopoiesis. Its receptor, Flt3, is expressed on myeloid, lymphoid and dendritic cell progenitors and is considered an important growth and differentiation factor for several hematopoietic lineages. Activating mutations of Flt3 are frequently found in acute myeloid leukemia (AML) patients and associated with a poor clinical prognosis. In the present review we provide an overview of our current knowledge on the role of FL in the generation of blood cell lineages. We examine recent studies on Flt3 expression by hematopoietic stem cells and its potential instructive action at early stages of hematopoiesis. In addition, we review current findings on the role of mutated FLT3 in leukemia and the development of FLT3 inhibitors for therapeutic use to treat AML. The importance of mouse models in elucidating the role of Flt3-ligand in normal and malignant hematopoiesis is discussed.
细胞因子Fms样酪氨酸激酶3配体（FL）是造血的重要调节因子。其受体Flt3在髓系、淋巴系和树突状细胞祖细胞上表达，被认为是几种造血谱系的重要生长和分化因子。Flt3的激活突变在急性髓系白血病（AML）患者中经常发现，并与不良临床预后相关。在本综述中，我们概述了目前关于FL在血细胞谱系生成中作用的知识。我们研究了造血干细胞Flt3表达的最新研究及其在造血早期阶段的潜在指导作用。此外，我们综述了关于突变型FLT3在白血病中的作用以及用于治疗AML的FLT3抑制剂的开发的当前研究结果。还讨论了小鼠模型在阐明Flt3配体在正常和恶性造血中的作用方面的重要性。
