Clinical Implications of Inflammation in Acute Myeloid Leukemia.

Clinical Implications of Inflammation in Acute Myeloid Leukemia.
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炎症在急性髓系白血病中的临床意义

DOI:
10.3389/fonc.2021.623952
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发表时间:
2021
影响因子:
4.7
通讯作者:
Récher C
Récher C
中科院分区:
医学3区
文献类型:
--
作者:
Récher C

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近年来,对急性髓系白血病肿瘤微环境的描述,包括对白血病干细胞生态位和克隆进化的全面分析,表明炎症可能在急性髓系白血病(AML)的多个方面发挥重要作用,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疾病中的潜在作用,与急性淋巴细胞白血病相比,糖皮质激素经典地被描述为类固醇耐药。此外,一些突变的癌基因,如RUNX1、NPM1或SRSF2,在转录上调节细胞状态,从而启动白血病细胞对糖皮质激素的敏感性。在临床实践中,血清铁蛋白或IL-6等炎症标志物对预后有很强的影响,并可能直接影响疾病的进展,而有趣的初步数据表明,地塞米松可能会改善白细胞计数高的AML患者的预后,这为开发评估糖皮质激素在AML中的作用的前瞻性临床试验铺平了道路。
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 RUNX1, NPM1, or SRSF2 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.
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