中医药通过调控DNA甲基化治疗恶性血液病：“态靶医学”新范式

Feng-lin SHEN; Yan-na ZHAO; Xiao-ling YU; Bo-lin WANG; Xiao-long WU; Gao-chen LAN; Rui-lan GAO

doi:10.1007/s11655-021-3316-7

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中医药通过调控DNA甲基化治疗恶性血液病：“态靶医学”新范式

Academic Exploration | Updated：2022-06-27

- 中医药通过调控DNA甲基化治疗恶性血液病：“态靶医学”新范式
- Chinese Medicine Regulates DNA Methylation to Treat Haematological Malignancies:A New Paradigm of "State-Target Medicine"
- Chinese Journal of Integrative Medicine 2022年28卷第6期页码：560-566
- Affiliations：
  
  Institute of Hematology Research, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou (310006),China
- Author bio：
  
  Prof. GAO Rui-lan, E-mail: gaoruilan@126.com
- Funds：
  
  the National Natural Science Foundation of China(81774068);the Natural Science Foundation of Zhejiang Province(LY20H290004);the Natural Science Foundation of Zhejiang Province (Youth Project)(LQ19H290002)
- DOI：10.1007/s11655-021-3316-7
  中图分类号：
- 纸质出版日期：2022-06-01，
  
  网络出版日期：2021-07-09，
  
  录用日期：2021-04-23
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Feng-lin SHEN, Yan-na ZHAO, Xiao-ling YU, 等. 中医药通过调控DNA甲基化治疗恶性血液病：“态靶医学”新范式[J]. Chinese Journal of Integrative Medicine, 2022,28(6):560-566.

Feng-lin SHEN, Yan-na ZHAO, Xiao-ling YU, et al. Chinese Medicine Regulates DNA Methylation to Treat Haematological Malignancies:A New Paradigm of "State-Target Medicine"[J]. Chinese Journal of Integrative Medicine, 2022,28(6):560-566.
Feng-lin SHEN, Yan-na ZHAO, Xiao-ling YU, 等. 中医药通过调控DNA甲基化治疗恶性血液病：“态靶医学”新范式[J]. Chinese Journal of Integrative Medicine, 2022,28(6):560-566. DOI： 10.1007/s11655-021-3316-7.

Feng-lin SHEN, Yan-na ZHAO, Xiao-ling YU, et al. Chinese Medicine Regulates DNA Methylation to Treat Haematological Malignancies:A New Paradigm of "State-Target Medicine"[J]. Chinese Journal of Integrative Medicine, 2022,28(6):560-566. DOI： 10.1007/s11655-021-3316-7.

摘要

DNA甲基化的调控异常对恶性血液病的发生发展具有重要影响

甲基化靶向治疗是现代医学的主要手段之一

但仍有诸多问题. 随着中医药对表观遗传学研究的不断进展和 "态靶医学" 理论的提出

这为形成现代医学 "攻靶" 与中医 "调态" 相结合的治疗新模式创造条件. 笔者讨论了中医证候和态势与DNA甲基化的相关联系

归纳了恶性血液病DNA甲基化的主要靶点和治疗现状

并梳理了中药有效组分和复方对其干预的最新研究

以期为恶性血液病的中西医 "态靶同调" 模式奠定理论基础

同时为临床诊治带来新的视角.

Abstract

Aberrant regulation of DNA methylation plays a crucial causative role in haematological malignancies (HMs). Targeted therapy

aiming for DNA methylation

is an effective mainstay of modern medicine; however

many issues remain to be addressed. The progress of epigenetic studies and the proposed theory of "state-target medicine" have provided conditions to form a new treatment paradigm that combines the "body state adjustment" of CM with targeted therapy. We discussed the correlation between Chinese medicine (CM) syndromes/states and DNA methylation in this paper. Additionally

the latest research findings on the intervention and regulation of DNA methylation in HMs

including the core targets

therapy status

CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of "state-target synchronous conditioning" pattern of integrative medicine for HMs

simultaneously leading a new perspective in clinical diagnosis and therapy.

关键词

Keywords

haematological malignanciesDNA methylationChinese medicinestate-target medicine

references

Navada SC, Steinmann J, Lübbert M, Silverman LR. Clinical development of demethylating agents in hematology. J Clin Invest 2014;124:40-46.

Tong XL. State target medicine: the future development of Chinese medicine. Chin J Integr Trad West Med (Chin)2021;41:16-18.

Schulz VP, Yan H, Lezon-Geyda K, An X, Hale J, Hillyer CD, et al. A unique epigenomic landscape defines human erythropoiesis. Cell Rep 2019;28:2996-3009.e7.

Lessard S, Beaudoin M, Benkirane K, Lettre G. Comparison of DNA methylation profiles in human fetal and adult red blood cell progenitors. Genome Med 2015;7:1-12.

Hogart A, Lichtenberg J, Ajay SS, Anderson S, Margulies EH, Bodine DM. Genome-wide DNA methylation profiles in hematopoietic stem and progenitor cells reveal overrepresentation of ETS transcription factor binding sites.Genome Res 2012;22:1407-1418.

Tu PS, Lin EC, Chen HW, Chen SW, Lin TA, Gau JP, et al. The extracellular signal-regulated kinase 1/2 modulates the intracellular localization of DNA methyltransferase 3A to regulate erythrocytic differentiation. Am J Transl Res 2020;12:1016-1030.

Zhang TJ, Zhang LC, Xu ZJ, Zhou JD. Expression and prognosis analysis of DNMT family in acute myeloid leukemia. Aging (Albany NY) 2020;12:14677-14690.

Anteneh H, Fang J, Song J. Structural basis for impairment of DNA methylation by the DNMT3A R882H mutation. Nat Commun 2020;11:2294.

Russler-Germain DA, Spencer DH, Young MA, Lamprecht TL, Miller CA, Fulton R, et al. The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell 2014;25:442-454.

Nguyen TV, Yao S, Wang Y, Rolfe A, Selvaraj A,Darman R, et al. The R882H DNMT3A hot spot mutation stabilizes the formation of large DNMT3A oligomers with low DNA methyltransferase activity. J Biol Chem 2019;294:16966-16977.

Khrabrova DA, Loiko AG, Tolkacheva AA, Cherepanova NA, Zvereva MI, Kirsanova OV, et al. Functional analysis of DNMT3A DNA methyltransferase mutations reported in patients with acute myeloid leukemia. Biomolecules 2020;10:8.

Sandoval JE, Huang YH, Muise A, Goodell MA, Reich NO. Mutations in the DNMT3A DNA methyltransferase in acute myeloid leukemia patients cause both loss and gain of function and differential regulation by protein partners. J Biol Chem 2019;294:4898-4910.

Haney SL, Upchurch GM, Opavska J, Klinkebiel D, Hlady RA, Suresh A, et al. Promoter hypomethylation and expression is conserved in mouse chronic lymphocytic leukemia induced by decreased or inactivated DNMT3a.Cell Rep 2016;15:1190-1201.

Hoang NM, Rui L. DNA methyltransferases in hematological malignancies. J Genet Genomics 2020;47:361-372.

Rau RE, Rodriguez BA, Luo M, Jeong M, Rosen A, Rogers JH, et al. DOT1L as a therapeutic target for the treatment of DNMT3A-mutant acute myeloid leukemia. Blood 2016;128:971-981.

Bledea R, Vasudevaraja V, Patel S, Stafford J, Serrano J, Esposito G, et al. Functional and topographic effects on DNA methylation in IDH1/2 mutant cancers. Sci Rep 2019;9:16830.

Gu Y, Yang R, Yang Y, Zhao Y, Wakeham A, Li WY, et al.IDH1 mutation contributes to myeloid dysplasia in mice by disturbing heme biosynthesis and erythropoiesis. Blood 2021;137:945-958.

Glass JL, Hassane D, Wouters BJ, Kunimoto H, Avellino R, Garrett-Bakelman FE, et al. Epigenetic identity in AML depends on disruption of nonpromoter regulatory elements and is affected by antagonistic effects of mutations in epigenetic modifiers. Cancer Discovery 2017;7:868-883.

Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI,Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 2016;374:2209-2221.

Ficz G, Branco MR, Seisenberger S, Santos F,Krueger F, Hore TA, et al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 2011;473:398-402.

Inokura K, Fujiwara T, Saito K, Iino T, Hatta S, Okitsu Y,et al. Impact of TET2 deficiency on iron metabolism in erythroblasts. Exp Hematol 2017;49:56-67.e5.

Ko M, Bandukwala HS, An J, Lamperti ED, Thompson EC, Hastie R, et al. Ten-eleven-translocation 2 (TET2)negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. Proc Natl Acad Sci U S A 2011;108:14566-14571.

Quivoron C, Couronné L, Della Valle V, Lopez CK, Plo I, Wagner-Ballon O, et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell 2011;20:25-38.

Bowman RL, Levine RL. TET2 in normal and malignant hematopoiesis. Cold Spring Harb Perspect Med 2017;7:a026518.

Poole CJ, Lodh A, Choi JH, van Riggelen J. MYC deregulates TET1 and TET2 expression to control global DNA (hydroxy) methylation and gene expression to maintain a neoplastic phenotype in T-ALL. Epigenetics Chromatin 2019;12:41.

Blecua P, Martinez-Verbo L, Esteller M. The DNA methylation landscape of hematological malignancies: an update. Mol Oncol 2020;14:1616-1639.

Dimopoulos K, Grønbaek K. Epigenetic therapy in hematological cancers. APMIS 2019;127:316-328.

Bates SE. Epigenetic therapies for cancer. N Engl J Med 2020;383:650-663.

Gou X, Gao Z, Yang Y, Li Q, Chen K, Lei Y, et al. State-target strategy: a bridge for the integration of Chinese and Western medicine. J Tradit Chin Med 2021;41:1-5.

Kelly AD, Kroeger H, Yamazaki J, Taby R, Neumann F, Yu S, et al. A CpG island methylator phenotype in acute myeloid leukemia independent of IDH mutations and associated with a favourable outcome. Leukemia 2017;31:2011-2019.

Wang J, Li F, Ma Z, Yu M, Guo Q, Huang J, et al. High expression of TET1 predicts poor survival in cytogenetically normal acute myeloid leukemia from two cohorts.EBioMedicine 2018;28:90-96.

Zeng YQ, Li WH, Zhang TE, Tan XJ, Qin J, Cui JM, et al.Study on the regulatory mechanism of immune-related gene CPG island in Kidney-yang deficiency syndrome.Lishizhen Med Mater Med Res (Chin) 2013;24:1515-1517.

Yao H, Mo S, Wang J, Li Y, Wang CZ, Wan JY, et al.Genome-wide DNA methylation profiles of phlegm-dampness constitution. Cell Physiol Biochem 2018;45:1999-2008.

Liu F, Xu RR. Study on the correlation between Chinese medical syndrome types and ID4 gene promoter methylation in human acute myeloid leukemia. Chin J Integr Tradit West Med (Chin) 2012;32:471-473.

Hu XQ, Su SB. An overview of epigenetics in Chinese medicine researches. Chin J Integr Med 2017;23:714-720.

Hassan FU, Rehman MS, Khan MS, Ali MA, Javed A,Nawaz A, et al. Curcumin as an alternative epigenetic modulator: mechanism of action and potential effects. Front Genet 2019;10:1-16.

Martín I, Navarro B, Solano C, Calabuig M, Hernández-Boluda JC, Amat P, et al. Synergistic antioncogenic activity of azacitidine and curcumin in myeloid leukemia cell lines and patient samples. Anticancer Res 2019;39:4757-4766.

Kedhari Sundaram M, Hussain A, Haque S, Raina R,Afroze N. Quercetin modifies 5'CpG promoter methylation and reactivates various tumor suppressor genes by modulating epigenetic marks in human cervical cancer cells. J Cell Biochem 2019;120:18357-18369.

Qing Y, Hu H, Liu Y, Feng T, Meng W, Jiang L, et al.Berberine induces apoptosis in human multiple myeloma cell line U266 through hypomethylation of p53 promoter.Cell Biol Int 2014;38:563-570.

Zhang RJ, Ma LM, Lu YJ, Bai B. Triptolide affect the methylation status of HL-60 cells. Chin J Hematol (Chin)2014;35:443-447.

Lee WY, Chen KC, Chen HY, Chen CY. Potential mitochondrial isocitrate dehydrogenase R140Q mutant inhibitor from traditional Chinese medicine against cancers.Biomed Res Int 2014;2014:364625.

Wang LP, Zhao YN, Sun X, Gao RL. Effects of bufalin on up-regulating methylation of Wilm's tumor 1 gene in human erythroid leukemic cells. Chin J Integr Med 2017;23:288-294.

Wang LP, Zhao YN, Gao RL. Resveratrol can reduce the expression of WT1 by methylation in K562 cells. Chin J Hematol (Chin) 2014;35:245-246.

Wang LP. The study of low-polarity ginsenoside ALK in regulating the methylation of WT1 gene in erythroleukemia cells in vivo and in vitro [Dissertation]. Hangzhou: Zhejiang Chinese Medical University; 2015.

Zhou QB, Yang XH, Wang HZ, Wang DX, Xu YG, Hu XM, et al. Effect of Qinghuang Powder combined with Bupi Yishen Decoction in treating patients with refractory cytopenia with multilineage dysplasia through regulating DNA methylation. Chin J Integr Med 2019;25:354-359.

Zhou QB, Zhu QZ, Wang HZ, Wang DX, Liu ZT, Xu YG, et al. Traditional Chinese medicine containing arsenic treated MDS patients effectively through regulating aberrant hypomethylation. Evid Based Complement Alternat Med 2020;2020:7469809.

Shen XH, Sun WL, Bao JZ, Hu MH, Wang J, Hu LY, et al. Clinical observation of "Jianpi Bushen Jiedu Recipe" in treating myelodysplastic syndrome. Acad J Shanghai Univ Tradit Chin Med (Chin) 2012;26:34-37.

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