Department of Hematology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Department of Hematology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa-shi, Chiba 277-8577, Japan.
Int J Mol Sci. 2022 Apr 23;23(9):4694. doi: 10.3390/ijms23094694.
KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting mutations are being developed. In acute myeloid leukemia (AML), genome profiling via next-generation sequencing has shown that several genes that are mutated in patients with AML impact patients' prognosis. Moreover, it was suggested that precision-medicine-based treatment using genomic data will improve treatment outcomes for AML patients. This paper presents (1) previous studies regarding the role of mutations in AML, (2) the data in AML with mutations from the HM-SCREEN-Japan-01 study, a genome profiling study for patients newly diagnosed with AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory AML, and (3) new therapies targeting mutations, such as tyrosine kinase inhibitors and heat shock protein 90 inhibitors. In this era when genome profiling via next-generation sequencing is becoming more common, mutations are attractive novel molecular targets in AML.
KIT 是一种 III 型受体酪氨酸激酶，有助于各种细胞中的细胞信号转导。由于 KIT 通过过度表达或突变而被激活，并在某些癌症（如胃肠道间质瘤和肥大细胞疾病）的发展中发挥重要作用，因此正在开发针对突变的分子治疗方法。在急性髓细胞白血病（AML）中，通过下一代测序进行的基因组分析表明，AML 患者中发生突变的几个基因会影响患者的预后。此外，有人建议使用基因组数据进行基于精准医学的治疗将改善 AML 患者的治疗结果。本文介绍了 (1) 突变在 AML 中的作用的先前研究，(2) 来自 HM-SCREEN-Japan-01 研究的 AML 中突变的数据，该研究是一项针对不适合标准一线治疗（不适合）或患有复发/难治性 AML 的新诊断 AML 患者的基因组分析研究，以及 (3) 针对突变的新疗法，如酪氨酸激酶抑制剂和热休克蛋白 90 抑制剂。在当今下一代测序进行基因组分析越来越普遍的时代，突变是 AML 中具有吸引力的新型分子靶标。
