Assumpção A L F V, Jark P C, Hong C C, Lu Z, Ruetten H M, Heaton C M, Pinkerton M E, Pan X
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Universidade Estadual Paulista Julio de Mesquita Filho-Campus de Jaboticabal, Jaboticabal, SP, Brazil.
J Vet Intern Med. 2018 Jan;32(1):361-369. doi: 10.1111/jvim.14860. Epub 2017 Nov 9.
The Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathways play important roles in the pathogenesis of diffuse large B cell lymphoma (DLBCL) in humans, and up-regulated STAT3 expression and activity are associated with worse clinical outcome in humans. No studies have evaluated the JAK-STAT signaling pathway in DLBCL of dogs.
STAT3 pathway is deregulated in DLBCL in dogs. We aim to assess the expression, activation, and cellular localization of STAT3 and mitogen-activated protein kinase ERK1/2 in DLBCL of dogs.
Forty-three client-owned dogs diagnosed with DLBCL by histopathology METHODS: Retrospective analysis of DLBCL in dogs, including patient characteristics and treatment, immunohistochemistry, and protein expressions by Western blot.
A higher percentage of STAT3 and p-STAT3 immunolabelled cells were observed in DLBCL of dogs when compared to normal canine lymph nodes. In STAT3 immunolabelled cells, STAT3 has higher nuclear expression in lymphoma samples than in normal or reactive lymph nodes. In addition to up-regulated STAT3 expression and activation, mitogen-activated kinase ERK1/2 activation is up-regulated in DLBCL of dogs.
Compared with the normal canine lymph node, DLBCL of dogs has up-regulated STAT3 pathway. Our results support future investigation of JAK inhibitors in the treatment of DLBCL in dogs.
Janus激酶(JAK)和信号转导及转录激活因子(STAT)通路在人类弥漫性大B细胞淋巴瘤(DLBCL)的发病机制中起重要作用,STAT3表达和活性上调与人类较差的临床结局相关。尚无研究评估犬DLBCL中的JAK-STAT信号通路。
犬DLBCL中STAT3通路失调。我们旨在评估犬DLBCL中STAT3和丝裂原活化蛋白激酶ERK1/2的表达、激活及细胞定位。
43只经组织病理学诊断为DLBCL的客户-owned犬
对犬DLBCL进行回顾性分析,包括患者特征和治疗、免疫组织化学以及蛋白质印迹法检测蛋白质表达。
与正常犬淋巴结相比,在犬DLBCL中观察到更高比例的STAT3和p-STAT3免疫标记细胞。在STAT3免疫标记细胞中,淋巴瘤样本中STAT3的核表达高于正常或反应性淋巴结。除了STAT3表达和激活上调外,犬DLBCL中丝裂原活化激酶ERK1/2的激活也上调。
与正常犬淋巴结相比,犬DLBCL中STAT3通路上调。我们的结果支持未来对JAK抑制剂治疗犬DLBCL的研究。