Fasouli Eirini Sofia, Katsantoni Eleni
Basic Research Center, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
Front Cell Dev Biol. 2021 May 14;9:669363. doi: 10.3389/fcell.2021.669363. eCollection 2021.
Hematopoietic stem cells (HSCs) produce all the terminally differentiated blood cells and are controlled by extracellular signals from the microenvironment, the bone marrow (BM) niche, as well as intrinsic cell signals. Intrinsic signals include the tightly controlled action of signaling pathways, as the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Activation of JAK-STAT leads to phosphorylation of members of the STAT family to regulate proliferation, survival, and self-renewal of HSCs. Mutations in components of the JAK-STAT pathway are linked with defects in HSCs and hematologic malignancies. Accumulating mutations in HSCs and aging contribute to leukemia transformation. Here an overview of hematopoiesis, and the role of the JAK-STAT pathway in HSCs and in the promotion of leukemic transformation is presented. Therapeutic targeting of JAK-STAT and clinical implications of the existing research findings are also discussed.
造血干细胞（HSCs）产生所有终末分化的血细胞，并受来自微环境、骨髓（BM）生态位的细胞外信号以及内在细胞信号的控制。内在信号包括信号通路的严格调控作用，如Janus激酶-信号转导和转录激活因子（JAK-STAT）通路。JAK-STAT的激活导致STAT家族成员磷酸化，以调节造血干细胞的增殖、存活和自我更新。JAK-STAT通路成分的突变与造血干细胞缺陷和血液系统恶性肿瘤有关。造血干细胞中不断积累的突变和衰老促成白血病转化。本文概述了造血过程，以及JAK-STAT通路在造血干细胞和白血病转化促进中的作用。还讨论了JAK-STAT的治疗靶点以及现有研究结果的临床意义。
