Abstract At present, acute myeloid leukemia (AML) accounts for about 15%-20% of childhood acute leukemia. Although overall survival rate is increasing with the help of risk stratification, stratification of chemotherapy, and supportive treatment, conventional pharmacotherapy still has a limited clinical effect and certain limitations in improving remission rate in previously untreated patients and reducing recurrence after remission. With the development of precision medicine, the mechanisms of targeted therapy, including abnormal activation of AML-related signaling pathways and epigenetic modifcation, have been found in recent years. Molecular-targeted drugs can therefore act on specifc receptors and target genes to improve clinical effect and the prognosis of AML patients.
Sakamoto KM, Grant S, Saleiro D, et al. Targeting novel signaling pathways for resistant acute myeloid leukemia[J]. Mol Genet Metab, 2015, 114(3):397-402.
[2]
Annesley CE, Brown P. Novel agents for the treatment of childhood acute leukemia[J]. Ther Adv Hematol, 2015, 6(2):61-79.
[3]
Wu H, Wang A, Qi Z, et al. Discovery of a highly potent FLT3 kinase inhibitor for FLT3-ITD-positive AML[J]. Leukemia, 2016, 30(10):2112-2116.
[4]
Dany M, Gencer S, Nganga R, et al. Targeting FLT3-ITD signaling mediates ceramide-dependent mitophagy and attenuates drug resistance in AML[J]. Blood, 2016, 128(15):1944-1958.
[5]
Bernasconi P, Boni M, Cavigliano PM, et al. Molecularly targeted therapy in acute myeloid leukemia[J]. Ann N Y Acad Sci, 2016, 1028(6):409-422.
[6]
Dombret H, Gardin C. An update of current treatments for adult acute myeloid leukemia[J]. Blood, 2016, 127(1):53-61.
[7]
Stein EM. Molecularly targeted therapies for acute myeloid leukemia[J]. Hematology Am Soc Hematol Educ Program, 2015, 2015(1):579-583.
[8]
Cooper TM, Cassar J, Eckroth E, et al. A phase I study of quizartinib combined with chemotherapy in relapsed childhood leukemia:a therapeutic advances in childhood leukemia & lymphoma (TACL) study[J]. Clin Cancer Res, 2016, 22(16):4014-4022.
[9]
Kadia TM, Ravandi F, Cortes J, et al. New drugs in acute myeloid leukemia[J]. Ann Onco, 2016, 27(5):770-778.
[10]
Lee LY, Hernandez D, Rajkhowa T, et al. Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor[J]. Blood, 2017, 129(2):257-260.
[11]
Yamada A, Moritake H, Kinoshita M, et al. Relapsed childhood acute myeloid leukemia patient with inversion of chromosome 16 harboring a low FLT3 internal tandem duplication allelic burden and KIT mutations[J]. Pediatr Int, 2016, 58(9):905-908.
[12]
Lin PH, Li HY, Fan SC, et al. A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia:implications for clinical practice[J]. Cancer Med, 2017, 6(2):349-360.
[13]
Kolb EA, Meshinchi S. Acute myeloid leukemia in children and adolescents:identifcation of new molecular targets brings promise of new therapies[J]. Hematol, 2015, 2015(1):507-513.
[14]
DiNardo CD, Cortes JE. New treatment for acute myelogenous leukemia[J]. Expert Opinion Pharmacother, 2015, 16(1):95-106.
[15]
Chen WC, Yuan JS, Xing Y, et al. An integrated analysis of heterogeneous drug responses in acute myeloid leukemia that enables the discovery of predictive biomarkers[J]. Cancer Res, 2016, 76(5):1214-1224.
[16]
Gjertsen BT, Schöffski P. Discovery and development of the Polo-like kinase inhibitor volasertib in cancer therapy[J]. Leukemia, 2015, 29(1):11-19.
[17]
Helmke C, Becker S, Strebhardt K. The role of Plk3 in oncogenesis[J]. Oncogene, 2016, 35(2):135-147.
[18]
Durlacher CT, Li ZL, Chen XW, et al. An update on the pharmacokinetics and pharmacodynamics of alisertib, a selective Aurora kinase A inhibitor[J]. Clin Exp Pharmacol Physiol, 2016, 43(6):585-601.
[19]
Fathi AT, Wander SA, Blonquist TM, et al. Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia[J]. Haematologica, 2017, 102(4):719-727.
[20]
Csizmar CM, Kim D, Sachs Z. The role of the proteasome in AML[J]. Blood Cancer J, 2016, 6(12):e503.
[21]
Aplenc R, Meshinchi S, Sung L, et al. The addition of bortezomib to standard chemotherapy for pediatric acute myeloid leukemia has increased toxicity without therapeutic beneft:a report from the Children's Oncology Group[J]. Blood, 2016, 128(22):899.
[22]
Larrue C, Saland E, Boutzen H, et al. Proteasome inhibitors induce FLT3-ITD degradation through autophagy in AML cells[J]. Blood, 2016, 127(7):882-892.
[23]
Wartman LD, Fiala MA, Fletcher T, et al. A phase I study of carflzomib for relapsed or refractory acute myeloid and acute lymphoblastic leukemia[J]. Leuk Lymphoma, 2016, 57(3):728-730.
[24]
Yen CY, Huang HW, Shu CW, et al. DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers[J]. Cancer Lett, 2016, 373(2):185-192.
[25]
Falini B, Sportoletti P, Brunetti L, et al. Perspectives for therapeutic targeting of gene mutations in acute myeloid leukaemia with normal cytogenetics[J]. Br J Haematol, 2015, 170(3):305-322.
[26]
Gill H, Man C, Ip AH, et al. Azacitidine as post-remission consolidation for sorafenib-induced remission of Fms-like tyrosine kinase-3 internal tandem duplication positive acute myeloid leukemia[J]. Haematologica, 2015, 100(7):e250-e253.
[27]
Blum W, Sanford BL, Klisovic R, et al. Maintenance therapy with decitabine in younger adults with acute myeloid leukemia in first remission:a phase 2 Cancer and Leukemia Group B Study (CALGB 10503)[J]. Leukemia, 2017, 31(1):34-39.
[28]
Nebbioso A, Benedetti R, Conte M, et al. Genetic mutations in epigenetic modifers as therapeutic targets in acute myeloid leukemia[J]. Expert Opin Ther Targets, 2015, 19(9):1187-1202.
[29]
Wouters BJ, Delwel R. Epigenetics and approaches to targeted epigenetic therapy in acute myeloid leukemia[J]. Blood, 2016, 127(1):42-52.
[30]
Tsai CT, So CW. Epigenetic therapies by targeting aberrant histone methylome in AML:molecular mechanisms, current preclinical and clinical development[J]. Oncogene, 2016, 36(13):1753-1759.
[31]
Morera L, Lübbert M, Jung M. Ta rgeting histone methyltransferases and demethylases in clinical trials for cancer therapy[J]. Clin Epigenetics, 2016, 8(1):57.
[32]
Cheng Y, Jia M, Chen Y, et al. Re-evaluation of various molecular targets located on CD34+CD38-Lin- leukemia stem cells and other cell subsets in pediatric acute myeloid leukemia[J]. Oncol Let, 2016, 11(1):891-897.
[33]
Tarlock K, Alonzo TA, Gerbing RB, et al. Gemtuzumab ozogamicin reduces relapse risk in FLT3/ITD acute myeloid leukemia:a report from the Children's Oncology Group[J]. Clin Cancer Res, 2016, 22(8):1951-1957.
[34]
Olombel G, Guerin E, Guy J, et al. The level of blast CD33 expression positively impacts the effect of gemtuzumab ozogamicin in patients with acute myeloid leukemia[J]. Blood, 2016, 127(17):2157-2160.
[35]
Pollard JA, Loken M, Gerbing RB, et al. CD33 expression and its association with gemtuzumab ozogamicin response:results from the randomized phase Ⅲ Children's Oncology Group trial AAML0531[J]. J Clin Oncol, 2016, 34(7):747-755.
[36]
Rashidi A, Walter RB. Antigen-specific immunotherapy for acute myeloid leukemia:where are we now, and where do we go from here[J]. Exp Rev Hematol, 2016, 9(4):335-350.
[37]
Reusch U, Harrington KH, Gudgeon CJ, et al. Characterization of CD33/CD3 tetravalent bispecifc tandem diabodies (TandAbs) for the treatment of acute myeloid leukemia[J]. Clin Cancer Res, 2016, 22(23):5829-5838.
[38]
Harrington KH, Gudgeon CJ, Laszlo GS, et al. The broad antiAML activity of the CD33/CD3 BiTE antibody construct, AMG 330, is impacted by disease stage and risk[J]. PLoS One, 2015, 10(8):e135945.
[39]
Al-Hussaini M, Rettig MP, Ritchey JK, et al. Targeting CD123 in acute myeloid leukemia using a T-cell-directed dual-affnity retargeting platform[J]. Blood, 2016, 127(1):122-131.
[40]
Chien CD, Sauter CT, Ishii K, et al. Preclinical development of FLT3-redirected chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia[J]. Blood, 2016, 128(22):1072.
[41]
Krupka C, Kufer P, Kischel R, et al. Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3 BiTE antibody construct AMG 330:reversing a T-cell-induced immune escape mechanism[J]. Leukemia, 2016, 30(2):484-491.
[42]
Wei A, Tan P, Perruzza S, et al. Maintenance lenalidomide in combination with 5-azacitidine as post-remission therapy for acute myeloid leukaemia[J]. Br J Haematol, 2015, 169(2):199-210.
[43]
Turtle CJ, Hanafi LA, Berger C, et al. CD19 CAR-T cells of defned CD4+:CD8+ composition in adult B cell ALL patients[J]. J Clin Invest, 2016, 126(6):2123-2138.
