Récher Christian
Service d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Université Toulouse III Paul Sabatier, Centre de Recherches en Cancérologie de Toulouse, Toulouse, France.
Front Oncol. 2021 Feb 22;11:623952. doi: 10.3389/fonc.2021.623952. eCollection 2021.
Recent advances in the description of the tumor microenvironment of acute myeloid leukemia, including the comprehensive analysis of the leukemic stem cell niche and clonal evolution, indicate that inflammation may play a major role in many aspects of acute myeloid leukemia (AML) such as disease progression, chemoresistance, and myelosuppression. Studies on the mechanisms of resistance to chemotherapy or tyrosine kinase inhibitors along with high-throughput drug screening have underpinned the potential role of glucocorticoids in this disease classically described as steroid-resistant in contrast to acute lymphoblastic leukemia. Moreover, some mutated oncogenes such as , , or transcriptionally modulate cell state in a manner that primes leukemic cells for glucocorticoid sensitivity. In clinical practice, inflammatory markers such as serum ferritin or IL-6 have a strong prognostic impact and may directly affect disease progression, whereas interesting preliminary data suggested that dexamethasone may improve the outcome for AML patients with a high white blood cell count, which paves the way to develop prospective clinical trials that evaluate the role of glucocorticoids in AML.
急性髓系白血病肿瘤微环境描述方面的最新进展,包括对白血病干细胞龛位和克隆进化的综合分析,表明炎症可能在急性髓系白血病(AML)的许多方面发挥主要作用,如疾病进展、化疗耐药和骨髓抑制。对化疗或酪氨酸激酶抑制剂耐药机制的研究以及高通量药物筛选,支持了糖皮质激素在这种传统上被描述为对类固醇耐药的疾病(与急性淋巴细胞白血病形成对比)中的潜在作用。此外,一些突变的癌基因,如 、 或 ,以一种使白血病细胞对糖皮质激素敏感的方式转录调节细胞状态。在临床实践中,血清铁蛋白或IL-6等炎症标志物具有很强的预后影响,可能直接影响疾病进展,而有趣的初步数据表明,地塞米松可能改善高白细胞计数的AML患者的预后,这为开展评估糖皮质激素在AML中作用的前瞻性临床试验铺平了道路。