大颗粒淋巴细胞白血病的发病机制与治疗
The pathogenesis and treatment of large granular lymphocyte leukemia.
作者信息
Steinway Steven Nathaniel, LeBlanc Francis, Loughran Thomas P
机构信息
Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
University of Virginia Cancer Center, University of Virginia, Charlottesville, VA, USA.
出版信息
Blood Rev. 2014 May;28(3):87-94. doi: 10.1016/j.blre.2014.02.001. Epub 2014 Mar 7.
Abstract
Large granular lymphocyte (LGL) leukemia is a spectrum of rare lymphoproliferative diseases of T lymphocytes and natural killer cells. These diseases frequently present with splenomegaly, neutropenia, and autoimmune diseases like rheumatoid arthritis. LGL leukemia is more commonly of a chronic, indolent nature; however, rarely, they have an aggressive course. LGL leukemia is thought to arise from chronic antigen stimulation, which drives long-term cell survival through the activation of survival signaling pathways and suppression of pro-apoptotic signals. These include Jak-Stat, Mapk, Pi3k-Akt, sphingolipid, and IL-15/Pdgf signaling. Treatment traditionally includes immunosuppression with low dose methotrexate, cyclophosphamide, and other immunosuppressive agents; however, prospective and retrospective studies reveal very limited success. New studies surrounding Jak-Stat signaling suggest this may reveal new avenues for LGL leukemia therapeutics.
摘要
大颗粒淋巴细胞（LGL）白血病是一种罕见的T淋巴细胞和自然杀伤细胞淋巴增殖性疾病谱。这些疾病常表现为脾肿大、中性粒细胞减少以及类风湿性关节炎等自身免疫性疾病。LGL白血病通常病程呈慢性、惰性；然而，极少数情况下会呈侵袭性病程。LGL白血病被认为源于慢性抗原刺激，这种刺激通过激活生存信号通路和抑制促凋亡信号来驱动细胞长期存活。这些信号通路包括Jak-Stat、Mapk、Pi3k-Akt、鞘脂和IL-15/Pdgf信号通路。传统治疗方法包括使用低剂量甲氨蝶呤、环磷酰胺和其他免疫抑制剂进行免疫抑制；然而，前瞻性和回顾性研究显示疗效非常有限。围绕Jak-Stat信号通路的新研究表明，这可能为LGL白血病的治疗开辟新途径。
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2
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