TGF-β/Smad信号通路与急性白血病

摘要/Abstract

摘要：

转化生长因子β（TGF-β）/Smad信号通路是人体细胞内的一种重要的信号通路，可调控细胞的生长、增殖与凋亡等生命活动，其信号转导由配体与受体结合、细胞质内信号通路、细胞核内相互作用三部分组成。该信号通路与急性白血病的发病机制、耐药、复发及预后密切相关，探究该信号通路的直接抑制剂、相关治疗靶点及天然提取物对白血病治疗的潜能，可为研究白血病的生物标志物和靶向基因治疗提供新思路。

关键词:转化生长因子β,白血病，急性,机制,疗法

Abstract:

Transforming growth factor-β（TGF-β）/Smad signaling pathway is an important signaling pathway in human cells， which can regulate life activities such as cell growth， proliferation and apoptosis， and its signal transduction consists of ligand and receptor binding， intracytoplasmic signaling pathway， as well as interactions within the cell nucleus. This signaling pathway is closely related to the pathogenesis， drug resistance， recurrence and prognosis of acute leukemia. Exploring the potential of direct inhibitors， related therapeutic targets and natural extracts of this signaling pathway for the treatment of leukemia can provide new ideas for the study of biomarkers and targeted gene therapy for leukemia.

Key words:Transforming growth factor beta,Leukemia, acute,Etiology,Therapeutics

王军, 贾秀红. TGF-β/Smad信号通路与急性白血病[J]. 国际肿瘤学杂志, 2023, 50(8): 498-502.

Wang Jun, Jia Xiuhong. TGF-β/Smad signal pathway and acute leukemia[J]. Journal of International Oncology, 2023, 50(8): 498-502.

参考文献37

[1]	Huang CH, Liao YJ, Chiou TJ, et al. TGF-β regulated leukemia cell susceptibility against NK targeting through the down-regulation of the CD48 expression[J].Immunobiology,2019,224(5): 649-658. DOI:10.1016/j.imbio.2019.07.002.
[2]	Wang X, Dong F, Zhang S, et al. TGF-β1 negatively regulates the number and function of hematopoietic stem cells[J].Stem Cell Reports,2018,11(1): 274-287. DOI:10.1016/j.stemcr.2018.05.017. pmid:29937145
[3]	David CJ, Massagué J. Contextual determinants of TGFβ action in development, immunity and cancer[J].Nat Rev Mol Cell Biol,2018,19(7): 419-435. DOI:10.1038/s41580-018-0007-0.
[4]	Shi Y, Massagué J. Mechanisms of TGF-β signaling from cell membrane to the nucleus[J].Cell,2003,113(6): 685-700. DOI:10.1016/S0092-8674(03)00432-X.
[5]	Zhang YE. Non-smad signaling pathways of the TGF-β family[J].Cold Spring Harb Perspect Biol,2017,9(2): a022129. DOI:10.1101/cshperspect.a022129.
[6]	Peters C, Meyer A, Kouakanou L, et al. TGF-β enhances the cytotoxic activity of Vδ2 T cells[J].Oncoimmunology,2019,8(1): e1522471. DOI:10.1080/2162402X.2018.1522471.
[7]	Beatson RE, Parente-Pereira AC, Halim L, et al. TGF-β1 potentiates Vγ9Vδ2 T cell adoptive immunotherapy of cancer[J].Cell Rep Med,2021,2(12): 100473. DOI:10.1016/j.xcrm.2021.100473.
[8]	陈文婷, 黄莹, 潘艳萍, 等. TGFβ1在急性髓系白血病中的异常表达及其对白血病细胞的调控[J].海南医学院学报,2022,28(24): 1889-1895, 1903. DOI:10.13210/j.cnki.jhmu.20221011.001.
[9]	El-Asmi F, El-Mchichi B, Maroui MA, et al. TGF-β induces PML SUMOylation, degradation and PML nuclear body disruption[J].Cytokine,2019,120: 264-272. DOI:10.1016/j.cyto.2019.05.008. pmid:31153006
[10]	Dahariya S, Raghuwanshi S, Sangeeth A, et al. Megakaryoblastic leukemia: a study on novel role of clinically significant long non-coding RNA signatures in megakaryocyte development during treatment with phorbol ester[J].Cancer Immunol Immunother,2021,70(12): 3477-3488. DOI:10.1007/s00262-021-02937-0.
[11]	Liu SX, Xiao HR, Wang GB, et al. Preliminary investigation on the abnormal mechanism of CD4⁺FOXP3⁺CD25^highregulatory T cells in pediatric B-cell acute lymphoblastic leukemia[J].Exp Ther Med,2018,16(2): 1433-1441. DOI:10.3892/etm.2018.6326.
[12]	El-maadawy EA, Elshal MF, Bakry RM, et al. Regulation of CD4⁺CD25⁺FOXP3⁺cells in pediatric acute lymphoblastic leukemia (ALL): implication of cytokines and miRNAs[J].Mol Immunol,2020,124: 1-8. DOI:10.1016/j.molimm.2020.05.002. pmid:32480291
[13]	Naghavi Alhosseini M, Palazzo M, Cari L, et al. Overexpression of potential markers of regulatory and exhausted CD8⁺T cells in the peripheral blood mononuclear cells of patients with B-acute lymphoblastic leukemia[J].Int J Mol Sci,2023,24(5): 4526. DOI:10.3390/ijms24054526.
[14]	Yu H, Huang T, Wang D, et al. Acute lymphoblastic leukemia-derived exosome inhibits cytotoxicity of natural killer cells by TGF-β signaling pathway[J].3 Biotech,2021,11(7): 313. DOI:10.1007/s13205-021-02817-5. pmid:34109098
[15]	Pan C, Liu P, Ma D, et al. Bone marrow mesenchymal stem cells in microenvironment transform into cancer-associated fibroblasts to promote the progression of B-cell acute lymphoblastic leukemia[J].Biomed Pharmacother,2020,130: 110610. DOI:10.1016/j.biopha.2020.110610. pmid:34321159
[16]	Pan C, Fang Q, Liu P, et al. Mesenchymal stem cells with cancer-associated fibroblast-like phenotype stimulate SDF-1/CXCR4 axis to enhance the growth and invasion of B-cell acute lymphoblastic leukemia cells through cell-to-cell communication[J].Front Cell Dev Biol,2021,9: 708513. DOI:10.3389/fcell.2021.708513.
[17]	Portale F, Cricrì G, Bresolin S, et al. ActivinA: a new leukemia-promoting factor conferring migratory advantage to B-cell precursor-acute lymphoblastic leukemic cells[J].Haematologica,2019,104(3): 533-545. DOI:10.3324/haematol.2018.188664. pmid:30262563
[18]	Portale F, Beneforti L, Fallati A, et al. Activin A contributes to the definition of a pro-oncogenic bone marrow microenvironment in t(12;21) preleukemia[J].Exp Hematol,2019,73: 7-12.e4. DOI:10.1016/j.exphem.2019.02.006. pmid:30825516
[19]	Yuan B, El Dana F, Ly S, et al. Bone marrow stromal cells induce an ALDH⁺stem cell-like phenotype and enhance therapy resistance in AML through a TGF-β-p38-ALDH2 pathway[J].PLoS One,2020,15(11): e0242809. DOI:10.1371/journal.pone.0242809.
[20]	Shingai Y, Yokota T, Okuzaki D, et al. Autonomous TGFβ signaling induces phenotypic variation in human acute myeloid leukemia[J].Stem Cells,2021,39(6): 723-736. DOI:10.1002/stem.3348. pmid:33539590
[21]	Vicioso Y, Gram H, Beck R, et al. Combination therapy for treating advanced drug-resistant acute lymphoblastic leukemia[J].Cancer Immunol Res,2019,7(7): 1106-1119. DOI:10.1158/2326-6066.CIR-19-0058. pmid:31138521
[22]	仲华, 林志强, 薄德映, 等. TGF-β1、GM-CSF及TNF-α对急性髓系白血病患者病情转归的评估[J].分子诊断与治疗杂志,2021,13(5): 807-810, 815. DOI:10.19930/j.cnki.jmdt.2021.05.032.
[23]	陈文婷, 姚红霞, 吴从明, 等. TGFβ1及VEGF基因在急性髓系白血病患者中的表达水平及其临床预后价值[J].中国实验血液学杂志,2020,28(1): 130-135. DOI:10.19746/j.cnki.issn1009-2137.2020.01.022.
[24]	雷永兰, 牛敏, 李靖, 等. NLR联合血清β2-MG、TGF-β1对急性髓系白血病的预后分析价值[J].临床血液学杂志,2021,34(10): 728-731. DOI:10.13201/j.issn.1004-2806.2021.10.011.
[25]	任丽蓉, 官晓红, 练颖, 等. 急性髓系白血病患者血清β2-MG、HGF、TGFβ1表达及临床意义[J].标记免疫分析与临床,2020,27(3): 488-492. DOI:10.11748/bjmy.issn.1006-1703.2020.03.029.
[26]	Zhang J, Zhang L, Cui H, et al. High expression levels of SMAD3 and SMAD7 at diagnosis predict poor prognosis in acute myeloid leukemia patients undergoing chemotherapy[J].Cancer Gene Ther,2019,26(5/6): 119-127. DOI:10.1038/s41417-018-0044-z.
[27]	Bataller A, Montalban-Bravo G, Soltysiak KA, et al. The role of TGFβ in hematopoiesis and myeloid disorders[J].Leukemia,2019,33(5): 1076-1089. DOI:10.1038/s41375-019-0420-1. pmid:30816330
[28]	杨丽媛, 汪路, 唐雨婷, 等. TGF-β信号通路抑制剂LY364947对急性髓系白血病细胞增殖、凋亡和侵袭的影响[J].中国细胞生物学学报,2019,41(2): 256-264.
[29]	Chen J, Mu Q, Li X, et al. Homoharringtonine targets Smad3 and TGF-β pathway to inhibit the proliferation of acute myeloid leukemia cells[J].Oncotarget,2017,8(25): 40318-40326. DOI:10.18632/oncotarget.16956. pmid:28454099
[30]	陈相言, 刘徽, 杨欢. 马钱苷元对白血病HL-60细胞生长及TGF-β1表达的影响[J].河北医药,2022,44(23): 3549-3553. DOI:10.3969/j.issn.1002-7386.2022.23.006.
[31]	王蕾, 李艳. p27^Kip1在As₂O₃诱导白血病细胞凋亡中的作用机制[J].现代肿瘤医学,2017,25(21): 3384-3389. DOI:10.3969/j.issn.1672-4992.2017.21.002.
[32]	王晓军, 茹甫毅, 吴双有, 等. 白藜芦醇对K562细胞COX-2、bFGF、TGFβ1及VEGF基因表达的影响[J].现代肿瘤医学,2017,25(10): 1549-1553. DOI:10.3969/j.issn.1672-4992.2017.10.009.
[33]	Bagheri P, Sharifi M, Ghadiri A. Downregulation of MIR100HG induces apoptosis in human megakaryoblastic leukemia cells[J].Indian J Hematol Blood Transfus,2021,37(2): 232-239. DOI:10.1007/s12288-020-01324-6.
[34]	Jiang M, Zou X, Huang W. Ecotropic viral integration site 1 regulates the progression of acute myeloid leukemia via MS4A3-mediated TGFβ/EMT signaling pathway[J].Oncol Lett,2018,16(2): 2701-2708. DOI:10.3892/ol.2018.8890. pmid:30013666
[35]	白琴, 汪嘉莉, 曾莉, 等. hsa-miR-23a-3p靶向TGFβ2对急性淋巴细胞白血病CEM/C1细胞增殖、凋亡、侵袭及细胞骨架重组的影响[J].广西医科大学学报,2021,38(12): 2265-2271. DOI:10.16190/j.cnki.45-1211/r.2021.12.011.
[36]	Erkeland SJ, Stavast CJ, Schilperoord-Vermeulen J, et al. The miR-200c/141-ZEB2-TGFβ axis is aberrant in human T-cell prolymphocytic leukemia[J].Haematologica,2022,107(1): 143-153. DOI:10.3324/haematol.2020.263756.
[37]	Xu D, Jiang J, He G, et al. miR-143-3p represses leukemia cell proliferation by inhibiting KAT6A expression[J].Anticancer Drugs,2022,33(1): e662-e669. DOI:10.1097/CAD.0000000000001231.