SOCS3解调对前体T细胞肿瘤中JAK/STAT途径的异常激活起着贡献。
SOCS3 deregulation contributes to aberrant activation of the JAK/STAT pathway in precursor T-cell neoplasms.
发表日期：2023 Feb 14
作者：
Antonio Lahera, Pilar López-Nieva, Hernán Alarcón, José L Marín-Rubio, María Á Cobos-Fernández, Pablo Fernández-Navarro, Agustín F Fernández, Laura Vela-Martín, Isabel Sastre, Sara Ruiz-García, Pilar Llamas, José L López-Lorenzo, Javier Cornago, Javier Santos, José Fernández-Piqueras, María Villa-Morales
来源：
BRITISH JOURNAL OF HAEMATOLOGY
摘要：
虽然Janus激酶/信号转导子与转录激活子(JAK/STAT)途径经常在T-ALL/LBL中发生改变，但尚未批准针对具有JAK/STAT组成信号的T-ALL/LBL患者的特定疗法，因此迫切需要确定可能是潜在治疗靶标的途径成员。在本研究中，我们寻找了通过异常甲基化调节的JAK/STAT途径成员，并确定SOCS3高甲基化是T-ALL/LBL中反复发生的事件之一。此外，我们研究了SOCS3失调在T-ALL/LBL中的影响，并证明SOCS3通过不同分子机制对抗JAK/STAT途径的组成活化。因此，SOCS3成为T-ALL/LBL的潜在治疗靶标。© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
Despite the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway being frequently altered in T-ALL/LBL, no specific therapy has been approved for T-ALL/LBL patients with constitutive signalling by JAK/STAT, so there is an urgent need to identify pathway members that may be potential therapeutic targets. In the present study, we searched for JAK/STAT pathway members potentially modulated through aberrant methylation and identified SOCS3 hypermethylation as a recurrent event in T-ALL/LBL. Additionally, we explored the implications of SOCS3 deregulation in T-ALL/LBL and demonstrated that SOCS3 counteracts the constitutive activation of the JAK/STAT pathway through different molecular mechanisms. Therefore, SOCS3 emerges as a potential therapeutic target in T-ALL/LBL.© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.