通过靶向突变的异柠檬酸脱氢酶1（IDH1）改善急性髓系白血病（AML）在前期骨髓增殖性肿瘤（MPN）基础上的治疗结果。
Advancing the outcomes of AML out of antecedent MPN by targeting mutated IDH1.
作者信息
Pratz Keith W
机构信息
Hospital of University of Pennsylvania, Philadelphia, Pennsylvania, USA.
出版信息
Br J Haematol. 2025 Apr;206(4):1250-1252. doi: 10.1111/bjh.19959. Epub 2024 Dec 22.
Abstract
Outcomes of myeloproliferative neoplasms (MPN)-associated acute leukaemias are dismal with conventional therapy. Approximately 20% of MPN-associated acute leukaemias have mutations in isocitrate dehydrogenase (IDH). Olutasidenib, and inhibitor of IDH1, demonstrates important clinical benefits in MPN-associated leukaemia with IDH1 mutation. Commentary on: Botton et al. Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukemia arising from a prior myeloproliferative neoplasm. Br J Haematol 2025; 206:1121-1128.
摘要
骨髓增殖性肿瘤（MPN）相关的急性白血病采用传统疗法的预后很差。约20%的MPN相关急性白血病存在异柠檬酸脱氢酶（IDH）突变。IDH1抑制剂奥芦他定尼在伴有IDH1突变的MPN相关白血病中显示出重要的临床益处。评论：博顿等人。奥芦他定尼在先前骨髓增殖性肿瘤引起的IDH1突变型急性髓系白血病中显示出显著的临床活性。《英国血液学杂志》2025年；206:1121 - 1128。
相似文献
1
Advancing the outcomes of AML out of antecedent MPN by targeting mutated IDH1.通过靶向突变的异柠檬酸脱氢酶1（IDH1）改善急性髓系白血病（AML）在前期骨髓增殖性肿瘤（MPN）基础上的治疗结果。
Br J Haematol. 2025 Apr;206(4):1250-1252. doi: 10.1111/bjh.19959. Epub 2024 Dec 22.
2
Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm.奥拉帕尼在先前骨髓增殖性肿瘤引起的IDH1突变急性髓系白血病中显示出显著的临床活性。
Br J Haematol. 2025 Apr;206(4):1121-1128. doi: 10.1111/bjh.19944. Epub 2024 Dec 19.
3
Olutasidenib: a novel mutant IDH1 inhibitor for the treatment of relapsed or refractory acute myeloid leukemia.奥拉帕尼：一种新型的突变 IDH1 抑制剂，用于治疗复发或难治性急性髓系白血病。
Expert Rev Hematol. 2024 Jun;17(6):211-221. doi: 10.1080/17474086.2024.2354486. Epub 2024 May 21.
4
Outcome of patients with IDH1/2-mutated post-myeloproliferative neoplasm AML in the era of IDH inhibitors.异柠檬酸脱氢酶（IDH）抑制剂时代，IDH1/2突变的骨髓增殖性肿瘤后急性髓系白血病（AML）患者的预后
Blood Adv. 2020 Nov 10;4(21):5336-5342. doi: 10.1182/bloodadvances.2020001528.
5
Clinical characteristics and outcomes in patients with acute myeloid leukemia with concurrent FLT3-ITD and IDH mutations.伴有 FLT3-ITD 和 IDH 突变的急性髓系白血病患者的临床特征和结局。
Cancer. 2021 Feb 1;127(3):381-390. doi: 10.1002/cncr.33293. Epub 2020 Oct 29.
6
IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms.慢性期和急变期骨髓增殖性肿瘤中的 IDH1 和 IDH2 突变分析。
Leukemia. 2010 Jun;24(6):1146-51. doi: 10.1038/leu.2010.77. Epub 2010 Apr 22.
7
Olutasidenib alone or with azacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: phase 1 results of a phase 1/2 trial.奥拉帕尼单药或联合阿扎胞苷治疗 IDH1 突变的急性髓系白血病和骨髓增生异常综合征：1/2 期临床试验的 1 期结果。
Lancet Haematol. 2023 Jan;10(1):e46-e58. doi: 10.1016/S2352-3026(22)00292-7. Epub 2022 Nov 10.
8
Looking Beyond the Surface: Olutasidenib and Ivosidenib for Treatment of mIDH1 Acute Myeloid Leukemia.深入探究：奥拉帕尼联合伊维替尼治疗异柠檬酸脱氢酶 1 突变型急性髓系白血病。
Curr Treat Options Oncol. 2024 Nov;25(11):1345-1353. doi: 10.1007/s11864-024-01264-7. Epub 2024 Oct 16.
9
Acquired somatic mutations of isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) in preleukemic disorders.白血病前期疾病中异柠檬酸脱氢酶1和2（IDH1和IDH2）的获得性体细胞突变
Blood Cells Mol Dis. 2015 Mar;54(3):286-91. doi: 10.1016/j.bcmd.2014.11.017. Epub 2014 Nov 26.
10
IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication.IDH1 和 IDH2 突变是急性髓系白血病中常见的遗传改变，并且在伴有 NPM1 突变但无 FLT3 内部串联重复的核型正常急性髓系白血病中具有不良预后。
J Clin Oncol. 2010 Aug 1;28(22):3636-43. doi: 10.1200/JCO.2010.28.3762. Epub 2010 Jun 21.
本文引用的文献
1
Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm.奥拉帕尼在先前骨髓增殖性肿瘤引起的IDH1突变急性髓系白血病中显示出显著的临床活性。
Br J Haematol. 2025 Apr;206(4):1121-1128. doi: 10.1111/bjh.19944. Epub 2024 Dec 19.
2
Treatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era.当代加速/急变期骨髓增殖性肿瘤患者的治疗方法和结局。
Blood Adv. 2024 Jul 9;8(13):3468-3477. doi: 10.1182/bloodadvances.2024012880.
3
FDA Approval Summary: Ivosidenib in Combination with Azacitidine for Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia with an IDH1 Mutation.FDA 批准概要：ivosidenib 联合阿扎胞苷治疗新诊断的伴有 IDH1 突变的急性髓系白血病患者。
Clin Cancer Res. 2024 Apr 1;30(7):1226-1231. doi: 10.1158/1078-0432.CCR-23-2234.
4
A Phase Ib/II Study of Ivosidenib with Venetoclax ± Azacitidine in IDH1-Mutated Myeloid Malignancies.ivosidenib 联合 venetoclax ± 阿扎胞苷治疗 IDH1 突变型髓系恶性肿瘤的 Ib/II 期研究。
Blood Cancer Discov. 2023 Jul 5;4(4):276-293. doi: 10.1158/2643-3230.BCD-22-0205.
5
Response Rate, Event-Free Survival, and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia: US Food and Drug Administration Trial-Level and Patient-Level Analyses.新发急性髓系白血病的缓解率、无事件生存和总生存：美国食品和药物管理局试验水平和患者水平分析。
J Clin Oncol. 2022 Mar 10;40(8):847-854. doi: 10.1200/JCO.21.01548. Epub 2021 Dec 10.
6
An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults.一份关于成人骨髓增生异常/骨髓增殖性肿瘤（MDS/MPN）统一反应标准的国际联盟提案。
Blood. 2015 Mar 19;125(12):1857-65. doi: 10.1182/blood-2014-10-607341. Epub 2015 Jan 26.
7
IDH2 mutation-induced histone and DNA hypermethylation is progressively reversed by small-molecule inhibition.异柠檬酸脱氢酶2（IDH2）突变诱导的组蛋白和DNA高甲基化可通过小分子抑制作用逐渐逆转。
Blood. 2015 Jan 8;125(2):296-303. doi: 10.1182/blood-2013-10-533604. Epub 2014 Nov 14.
8
Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML.突变型 IDH1 在体内促进白血病发生，并且可以在人急性髓系白血病中被特异性靶向。
Blood. 2013 Oct 17;122(16):2877-87. doi: 10.1182/blood-2013-03-491571. Epub 2013 Aug 16.
9
IDH mutation impairs histone demethylation and results in a block to cell differentiation.IDH 突变会损害组蛋白去甲基化，导致细胞分化受阻。
Nature. 2012 Feb 15;483(7390):474-8. doi: 10.1038/nature10860.
10
Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation.白血病 IDH1 和 IDH2 突变导致超甲基化表型，破坏 TET2 功能，并损害造血分化。
Cancer Cell. 2010 Dec 14;18(6):553-67. doi: 10.1016/j.ccr.2010.11.015. Epub 2010 Dec 9.
Zotero 插件