山东大学学报 (医学版) ›› 2019, Vol. 57 ›› Issue (7): 6-12.doi: 10.6040/j.issn.1671-7554.0.2019.191
• • 上一篇
王建祥,顾闰夏
WANG Jianxiang, GU Runxia
摘要： 急性髓系白血病是一组高度异质性的克隆性疾病,既往以细胞毒药物为主的化疗方案是治疗的基本骨架,但已难以满足临床治疗需求。近年来,深度测序技术的发展和靶向药物的应用开启了急性髓系白血病靶向治疗的大门,也为急性髓系白血病的治疗带来了巨大的进步。随着研究的深入,靶向药物耐药、联合治疗毒性叠加、缺乏有效靶点等问题也逐渐凸显出来,为治疗策略选择提出了新的挑战。未来,深入探讨急性髓系白血病发病机制,开发和合理使用靶向药物和免疫治疗,将有望进一步提高急性髓系白血病疗效,推动其进入个体化精准治疗的新时代。
中图分类号:
| [1] Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia [J]. N Engl J Med, 2016, 374(23): 2209-2221. [2] Patel JP, Gonen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia [J]. N Engl J Med, 2012, 366(12): 1079-1089. [3] The Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia [J]. N Engl J Med, 2013, 368(22): 2059-2074. [4] Grimwade D, Mrozek K. Diagnostic and prognostic value of cytogenetics in acute myeloid leukemia [J]. Hematol Oncol Clin North Am, 2011, 25(6): 1135-1161. [5] Grimwade D, Ivey A, Huntly BJ. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance [J]. Blood, 2016, 127(1): 29-41. [6] Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation [J]. N Engl J Med, 2017, 377(5): 454-464. [7] Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel [J]. Blood, 2017, 129(4): 424-447. [8] NCCN. NCCN clinical practice guilelines in oncology: acute meyloid leukemia [J]. Version 1, 2019. [9] Rollig C, Serve H, Huttmann A, et al. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia(SORAML): a multicentre, phase 2, randomised controlled trial [J]. Lancet Oncol, 2015, 16(16): 1691-1699. [10] Perl AE, Altman JK, Cortes J, et al. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study [J]. Lancet Oncol, 2017, 18(8): 1061-1075. [11] Smith CC, Lasater EA, Lin KC, et al. Crenolanib is a selective type I pan-FLT3 inhibitor [J]. Proc Natl Acad Sci USA, 2014, 111(14): 5319-5324. [12] Cortes J, Khaled S, Martinelli G, et al. Quizartinib significantly prolongs overall survival in patients with FLT3-internal tandem duplication-mutated(mut)relapsed/refractory AML in the phase 3, randomized, controlled quantum-r trial [J]. EHA, 2018, LB2600. [13] Pratz K, Cherry M, Altman JK, et al. Preliminary results from a phase 1 study of gilteritinib in combination with induction and consolidation chemotherapy in subjects with newly diagnosed acute myeloid leukemia(AML)[J]. Blood, 2017, 130: 722. [14] Walter RB, Collins RH, Stone RM, et al. Addition of crenolanib to standard induction and consolidation therapies improved long-term outcomes in newly diagnosed FLT3 mutant AML patients ed acute myelo[J]. EHA, 2018, 227. [15] Abbas S, Lugthart S, Kavelaars FG, et al. Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value [J]. Blood, 2010, 116(12): 2122-2126. [16] Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate[J]. Nature, 2009, 462(7274): 739-744. [17] Figueroa ME, Abdel-Wahab O, Lu C, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation [J]. Cancer Cell, 2010, 18(6): 553-567. [18] Dinardo CD, Stein EM, Stéphane de Botton, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML [J]. N Engl J Med, 2018, 378(25): 2386-2398. [19] Levine RL, Flinn IW, Kantarjian HM, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia [J]. Blood, 2017, 130(6): 722-731. [20] Stein EM, Dinardo CD, Amir T, et al. Ivosidenib or enasidenib combined with induction and consolidation chemotherapy in patients with newly diagnosed AML with an IDH1 or IDH2 mutation is safe, effective, and leads to MRD-negative complete remissions [J]. Blood, 2018, 132: 560. [21] Pan RQ, Hogdal LJ, Benito JM, et al.Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia [J]. Cancer Discov, 2014, 4(3): 362-375. [22] Dinardo CD, Pratz KW, Letai A, et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study [J]. Lancet Oncol, 2018, 19(2): 216-228. [23] 张岩, 汤君宇, 张梅, 等. BCL-2抑制剂联合低剂量阿糖胞苷治疗异基因造血干细胞移植后复发老年急性髓系白血病一例报告并文献复习[J].中华血液学杂志, 2019, 40(2): 144-146. [24] Wei A, Strickland SA, Hou JZ, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study [J]. J Clin Oncol, 2019, 37(15): 1277-1284. [25] DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia [J]. Blood, 2019, 133(1): 7-17 [26] Cortes JE, Heidel FH, Heuser M, et al. A phase 2 randomized study of low dose Ara-C with or without glasdegib(PF-04449913)in untreated patients with acute myeloid leukemia or high-risk myelodysplastic syndrome [J]. Blood, 2016, 128: 99. [27] Minami Y, Minami H, Miyamoto T, et al. Phase I study of glasdegib(PF-04449913), an oral smoothened inhibitor, in Japanese patients with select hematologic malignancies [J]. Cancer Sci, 2017, 108(8): 1628-1633. [28] Hassan F, Oumedaly R, Emmanuel R, et al. Fractionated doses of gemtuzumab ozogamicin with escalated doses of daunorubicin and cytarabine as first acute myeloid leukemia salvage in patients aged 50-70-year old: a phase 1/2 study of the acute leukemia French association [J]. Am J Hematol, 2015, 87(1): 62-65. [29] Pautas Cécile, Raffoux E, Lambert J, et al. Outcomes following hematopoietic stem cell transplantation in patients treated with chemotherapy with or without gemtuzumab ozogamicin for acute myeloid leukemia [J]. Blood, 2018, 132: 28. [30] Castaigne S, Pautas C, Terr'e C, et al. Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia(ALFA-0701): a randomised, open-label, phase 3 study [J]. Lancet, 2012, 379(9825): 1508-1516. [31] Uy GL, Rettig MP, Vey N, et al. Phase 1 cohort expansion of flotetuzumab, a CD123×CD3 bispecific dart? protein in patients with relapsed/refractory acute myeloid leukemia(AML)[J]. Blood, 2018, 132: 764. [32] Friedrich M, Henn A, Raum T, et al. Preclinical characterization of AMG 330, a CD3/CD33-bispecific T-cell-engaging antibody with potential for treatment of acute myelogenous leukemia [J]. Mol Cancer Ther, 2014, 13(6): 1549-1557. [33] Ravandi F, Stein AS, Kantarjian HM, et al. A phase 1 first-in-human study of AMG 330, an anti-CD33 bispecific T-cell engager(BiTE)antibody construct, in relapsed/refractory acute myeloid leukemia(R/R AML)[J]. Blood, 2018, 132: 25. [34] Schlenk RF, Paschka P, Krzykalla J, et al. Gemtuzumab ozogamicin in NPM1-mutated acute myeloid leukemia(AML): results from the prospective randomized AMLSG 09-09 phase-III study [J]. Blood, 2018, 132: 81. [35] Lynn Q, David MD, Alison K, et al. Clonal heterogeneity of acute myeloid leukemia treated with the IDH2 inhibitor enasidenib [J]. Nat Med, 2018, 24(8): 1167-1177. [36] Tyner JW, Tognon CE, Bottomly D, et al. Functional genomic landscape of acute myeloid leukaemia [J]. Nature, 2018, 526: 526-531. [37] Daver NG, Pollyea DA, Garcia JS, et al. Safety, Efficacy, Pharmacokinetic(PK)and biomarker analyses of BCL2 inhibitor venetoclax(Ven)plus MDM2 inhibitor idasanutlin(idasa)in patients(pts)with relapsed or Refractory(R/R)AML: a phase Ib, non-randomized, open-label study [J]. Blood, 2018, 132: 767. [38] 米瑞华, 袁芳芳, 魏旭东. 急性髓系白血病免疫治疗新进展[J]. 白血病·淋巴瘤, 2019, 28(1): 12-16. MI Ruihua, YUAN Fangfang, WEI Xudong.Progress of immunotherapy of acute myelogenous leukemia[J]. Journal of Leukemia & Lymphoma, 2019, 28(1):12-16. [39] Jetani H, Cadenas IG, Nerreter T, et al. FLT3 inhibitor treatment increases FLT3 expression that exposes FLT3-ITD+ AML blasts to elimination by FLT3 CAR-T cells [J]. Blood, 2018, 132: 903. [40] Daver NG, Manero GG, Sreyashi Basu S, et al. Safety, efficacy, and biomarkers of response to azacitidine(AZA)with nivolumab(Nivo)and AZA with Nivo and ipilimumab(Ipi)in relapsed/refractory acute myeloid leukemia: a non-randomized, phase 2 study[J]. Blood, 2018, 132: 906. [41] 陈子兴. 急性髓系白血病的表观遗传调控异常和表观基因组景观改变及靶向治疗研究进展[J]. 中华血液学杂志, 2019, 40(1): 78-82. CHEN Zixing. The aberrant epigenetic regulation and epigenomic landscape alteration in human acute myelogenous leukemia and the emerged agents that target epigenetic regulators[J]. Chinese Journal of Hematology, 2019, 40(1):78-82. [42] Rashidi A, Uy GL. Targeting the microenviron-ment in acute myeloid leukemia [J]. Curr Hematol Malig Rep, 2015, 10(2): 126-131. [43] Brunner AM, Blonquist TM, Daniel J, et al. Phase II clinical trial of alisertib, an aurora kinase inhibitor, in combination with induction chemotherapy in high-risk, untreated patients with acute myeloid leukemia [J]. Blood, 2018, 132: 766. [44] Walker AR, Bhatnagar B, Marcondes A, et al. Interim results of a phase 1b/2 Study of entospletinib(GS-9973)monotherapy and in combination with chemotherapy in patients with acute myeloid leukemia [J]. Blood, 2016, 128: 2831. [45] Soliman HH, Minton SE, Han HS, et al. A phase I study of indoximod in patients with advanced malignancies [J]. Oncotarget, 2016, 7(16): 22928-22938. [46] Baker A, Gregory GP, Verbrugge I, et al. The CDK9 inhibitor dinaciclib exerts potent apoptotic and antitumor effects in preclinical models of MLL-rearranged acute myeloid leukemia [J]. Cancer Res, 2016, 76(5): 1158-1169. |
| [1] | 王福立,孙银萍,秦杰,荣建胜. DC-CIK细胞联合EGFR-TKI治疗35例老年晚期EGFR突变肺癌的效果[J]. 山东大学学报 (医学版), 2022, 60(7): 110-117. |
| [2] | 哈春芳,李茹月. 卵巢癌耐药机制与靶向治疗策略的研究进展[J]. 山东大学学报 (医学版), 2021, 59(9): 117-123. |
| [3] | 司海朋,张文灿,李乐,周鑫. Kümmell's病的危险因素和诊治研究进展[J]. 山东大学学报 (医学版), 2021, 59(6): 25-32. |
| [4] | 毕亚珍,冯洒然,李红,刘倩,于靖宜,王焱,朱传升. 以高钙血症为首发表现的成人急性髓系白血病1例报告[J]. 山东大学学报 (医学版), 2021, 59(5): 116-118. |
| [5] | 张晓慧,罗建民,索晓慧,孙国锋,李静. 抑癌基因SOCS1、SOCS3的甲基化与急性髓系白血病患者治疗转归及预后的关联分析[J]. 山东大学学报 (医学版), 2021, 59(3): 67-73. |
| [6] | 王艳,张宇卉,胡耐博,滕广帅,周圆,白洁. 基于单细胞测序分析急性髓系白血病患者骨髓免疫微环境的特点[J]. 山东大学学报 (医学版), 2021, 59(10): 30-38. |
| [7] | 焉传祝,王伟,纪坤乾,赵玉英. 线粒体与脑疾病[J]. 山东大学学报 (医学版), 2020, 1(8): 34-41. |
| [8] | 陈安静,张训. 靶向小类泛素化修饰的胶质瘤治疗新策略[J]. 山东大学学报 (医学版), 2020, 1(8): 88-94. |
| [9] | 黄晓军. 细胞免疫治疗在血液系统恶性肿瘤的应用进展[J]. 山东大学学报 (医学版), 2019, 57(7): 1-5. |
| [10] | 王海涛. 去势抵抗性前列腺癌精准治疗的研究进展[J]. 山东大学学报 (医学版), 2019, 57(1): 30-35. |
| [11] | 姜宝法,丁国永,刘雪娜. 暴雨洪涝与人类健康关系的研究进展[J]. 山东大学学报 (医学版), 2018, 56(8): 21-28. |
| [12] | 马润美,张翼,王彦文,许丹丹,孙志颖,石婉荧,崔亮亮,李湉湉. 大气颗粒物污染与血糖关系的系统综述[J]. 山东大学学报 (医学版), 2018, 56(11): 27-33. |
| [13] | 凌瑞,张聚良. 乳腺癌内分泌治疗的相关进展[J]. 山东大学学报 (医学版), 2018, 56(1): 27-31. |
| [14] | 王殊,彭媛. 从2017年美国临床肿瘤学会大会报告看早期乳腺癌治疗加减法[J]. 山东大学学报 (医学版), 2018, 56(1): 17-21. |
| [15] | 陈波,张磊. 2017年乳腺癌新辅助治疗进展[J]. 山东大学学报 (医学版), 2018, 56(1): 12-16. |
|
||
