急性髓系白血病（AML）是造血系统的恶性肿瘤，其特征是骨髓和外周组织中未成熟和非功能性白血病幼稚细胞的积累。从机制上讲，AML的发展可通过“两次打击”理论来解释，该理论基于驱动突变的积累，这些突变将相互合作以诱导转化。然而，相当一部分AML患者仅表现出一种驱动突变，因此，在这些病例中，淋巴细胞转化是如何发生的尚不清楚。累积的证据表明，非遗传因素，如慢性炎症，可能影响AML的发展，并且相应的临床数据表明，患有慢性炎症性疾病的患者发生造血系统恶性肿瘤的风险增加。在这里，我们使用小鼠慢性炎症模型，证明全身升高的细胞因子和趋化因子水平以及Jak/Stat3信号通路的超活化可能替代“第二次打击”突变，并加速肿瘤发生。总之，我们的数据强调了慢性炎症作为AML发展的另一个因素，提供了对转化机制的进一步了解，并为该疾病的治疗开辟了新的途径。版权所有 © 2023。由Elsevier Inc.出版。

Acute myeloid leukemia (AML) is a malignant neoplasia of the hematopoietic system characterized by the accumulation of immature and non-functional leukemic blasts in the bone marrow and peripheral tissues. Mechanistically, the development of AML is explained by the "two-hit" theory, based on the accumulation of driver mutations that will cooperate to induce transformation. However, a significant percentage of AML patients exhibit only one driver mutation, and thus, how leukemic transformation occurs in these cases is unclear. Accumulating evidence suggests that non-genetic factors, such as chronic inflammation, might influence AML development, and accordingly, clinical data reported that patients with chronic inflammatory disorders have an increased risk of developing hematological malignancies. Here, using a mouse model of chronic inflammation, we demonstrate that systemic elevated levels of cytokines and chemokines, and hyper-activation of the Jak/Stat3 signaling pathway, might substitute "second hit" mutations and accelerate tumorigenesis. Altogether, our data highlights chronic inflammation as an additional factor in the development of AML, providing additional understanding of the mechanisms of transformation, and opening new venues for the treatment of this disease.Copyright © 2023. Published by Elsevier Inc.