Department of Biology, Universidad Autónoma de Madrid, Madrid, Spain.
Department of Genome dynamics and function, Centro de Biología Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain.
Br J Haematol. 2023 May;201(4):718-724. doi: 10.1111/bjh.18694. Epub 2023 Feb 14.
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.
尽管 T-ALL/LBL 中经常改变 Janus 激酶/信号转导子和转录激活子（JAK/STAT）途径，但对于 JAK/STAT 组成性信号的 T-ALL/LBL 患者，尚无特定的治疗方法获得批准，因此迫切需要确定可能成为潜在治疗靶点的途径成员。在本研究中，我们搜索了可能通过异常甲基化调节的 JAK/STAT 途径成员，并确定 SOCS3 高甲基化为 T-ALL/LBL 中的一个复发性事件。此外，我们探讨了 SOCS3 失调在 T-ALL/LBL 中的意义，并证明 SOCS3 通过不同的分子机制拮抗 JAK/STAT 途径的组成性激活。因此，SOCS3 成为 T-ALL/LBL 中的一个潜在治疗靶点。
