急性髓系白血病（AML）是一种血液恶性肿瘤，其特征是骨髓中未成熟髓系细胞的异常增殖和积聚。炎症在 AML 进展中起着至关重要的作用，但细胞内在炎症通路的过度激活也会引发细胞死亡。 IRF2BP2 是一种与 AML 发病机制有关的染色质调节因子，尽管其在这种疾病中的确切作用尚不完全清楚。在这项研究中，我们证明 IRF2BP2 与 AP-1 异二聚体 ATF7/JDP2 相互作用，后者参与激活 AML 细胞中的炎症途径。我们发现 IRF2BP2 被 ATF7/JDP2 二聚体招募到染色质并抵消其基因激活功能。 IRF2BP2 的缺失会导致炎症通路过度激活，从而导致增殖大幅减少。我们的研究表明，激活和抑制转录机制之间的精确平衡在 AML 细胞中创造了促癌炎症环境。 ATF7/JDP2-IRF2BP2 调节轴可能是该过程的关键调节因子，因此可能代表 AML 的有前途的治疗脆弱性。因此，我们的研究为 AML 发病机制的分子机制提供了新的见解，并确定了 AML 治疗的潜在治疗靶点。© 作者 2024。由牛津大学出版社代表 Nucleic Acids Research 出版。

Acute myeloid leukemia (AML) is a hematological malignancy characterized by abnormal proliferation and accumulation of immature myeloid cells in the bone marrow. Inflammation plays a crucial role in AML progression, but excessive activation of cell-intrinsic inflammatory pathways can also trigger cell death. IRF2BP2 is a chromatin regulator implicated in AML pathogenesis, although its precise role in this disease is not fully understood. In this study, we demonstrate that IRF2BP2 interacts with the AP-1 heterodimer ATF7/JDP2, which is involved in activating inflammatory pathways in AML cells. We show that IRF2BP2 is recruited by the ATF7/JDP2 dimer to chromatin and counteracts its gene-activating function. Loss of IRF2BP2 leads to overactivation of inflammatory pathways, resulting in strongly reduced proliferation. Our research indicates that a precise equilibrium between activating and repressive transcriptional mechanisms creates a pro-oncogenic inflammatory environment in AML cells. The ATF7/JDP2-IRF2BP2 regulatory axis is likely a key regulator of this process and may, therefore, represent a promising therapeutic vulnerability for AML. Thus, our study provides new insights into the molecular mechanisms underlying AML pathogenesis and identifies a potential therapeutic target for AML treatment.© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.