K-562

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K-562人類永生化骨髓性白血病細胞系英语Immortalised cell line,處於高度未分化狀態,並且屬於紅白血病(erythroleukemia)細胞系,具有惡性程度高、增殖速度快,以及可被一系列體外誘導劑誘導分化的特點[1]。最初分離自一名處於急性期的53歲女性慢性骨髓性白血病(CML)患者的胸水[2][3]

特徵[编辑]

K-562細胞不粘連且圓形,對bcr:abl融合基因呈陽性反應,並且與未進行細胞分化粒細胞[4]紅細胞[5]蛋白質組相似。在細胞培養的過程中,它們的結塊比許多其他懸浮細胞系要少得多,原因可能是由於細胞表面粘附分子引起的bcr:abl融合基因下調[6]。然而有研究表明,過度表達bcr:abl融合基因可能會增加細胞對細胞培養皿的粘附力[7]

K-562細胞可以自發形成類似於早期紅細胞粒細胞單核細胞的特徵[8],並且由於缺乏抑制自然殺傷細胞活性所需的主要組織相容性複合體[3],因此很容易被自然殺傷細胞殺死[9] 。它們也沒有任何痕量的愛潑斯坦-巴爾病毒和其他皰疹病毒。除了費城染色體外,它們在15號染色體的長臂與17號染色體之間表現出第二種的相互易位[2]。 K-562細胞有兩個子系可以表示MHC1類分子A2[10]和A3[11]

細胞週期與調控[编辑]

在生長、細胞分化和凋亡方面,許多因素和成分在K-562細胞的細胞週期中發揮作用[12]。這些白血病細胞的生長受到細胞分化或凋亡的控制[13]。這些未分化的祖細胞中的脫乙酰基酶活性可以誘導細胞分化,從而改變K-562細胞的表型和形態[12]。這些變化還可以使白血病細胞進入應激狀態,從而提高細胞對引發凋亡的藥物的敏感性[12]。此外,表型的變化會降低生長速率,並且導致K562細胞具有能夠向紅細胞系、粒細胞系、單核細胞-巨噬細胞系統和巨核細胞系統分化的潛能,表現出相應的細胞表型[14][15],能夠在低氧環境下被誘導分化形成紅細胞和巨核細胞,故而是用於研究紅系誘導分化的理想細胞模型,目前已經成為研究細胞分化的主要細胞模型[16][17]

K-562細胞及許多癌細胞均存在着Aurora激酶英语Aurora kinase過多的問題[18]。Aurora激酶在紡錘體形成、染色體分離及胞質分裂中都發揮作用[18] ,而這些功能在細胞中是必需的,以便分裂和再生組織,並且起維持穩態的作用。然而過度表達Aurora激酶會導致細胞分裂時不受控制,從而導致癌症[18] 。因此,抑制Aurora激酶是癌症的重要調控機制,因為它可以防止細胞進行有絲分裂[18]

細胞凋亡是調節K-562細胞的重要機制,並且可通過細胞代謝狀態的變化來誘導[12]。細胞凋亡過程中涉及許多不同的細胞成分,例如BCR/ABL、Bcl-2英语Bcl-2Bax英语Bcl-2-associated X protein蛋白和細胞色素c[13],而p53蛋白在K-562細胞的細胞週期調控中也十分重要[19],因為它靶向細胞週期蛋白依賴性激酶抑製劑p21英语p21,引起細胞分化、細胞週期停滯在G1期,最終導致細胞凋亡[19]。當這些成分的水平降低時,它們將不能抑制癌細胞的凋亡,或者會導致細胞凋亡被誘導[13] 。這些成分是線粒體中的關鍵因素,因此有證據支持細胞凋亡會使用到線粒體凋亡途徑[13]。除此之外,當這些細胞成分偏離平衡點時,就會令細胞的形態出現變化,導致K-562細胞停滯在G2/M期[13],從而導致核碎裂、染色質濃縮和其他形態學變化,最終導致細胞程序性死亡[13]

目前已知伊馬替尼可以抑制BCR/ ABL,導致細胞停止生長並開始凋亡[20]。K-562細胞的另一個重要調節器是Sirtuin英语Sirtuin[12],通過與細胞中的脫乙酰酶活性相互作用而在細胞應激、代謝和自噬中發揮作用[12]。其他調節K-562細胞的方法包括重樓皂苷 D(polyphyllin D),它會令細胞從祖細胞狀態中進行分化並開始凋亡[13]

參考資料[编辑]

  1. ^ Fader, CM; Salassa, BN; Grosso, RA; Vergara, AN; Colombo, MI. Hemin induces mitophagy in a leukemic erythroblast cell line.. Biology of the cell. 2016-04, 108 (4): 77–95 [2020-02-13]. PMID 26773440. doi:10.1111/boc.201500058. 
  2. ^ 2.0 2.1 Lozzio, C.B.; Lozzio, B.B., Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome, Blood, 1975, 45 (3): 321–34, PMID 163658 
  3. ^ 3.0 3.1 Drexler, H.G., The Leukemia-Lymphoma Cell Line Factsbook, San Diego: Academic Press, 2000 
  4. ^ Klein, E.; Ben-Bassat, H.; Neumann, H.; Ralph, P.; Zeuthen, J.; Polliack, A.; Vánky, F., Properties of the K562 cell line, derived from a patient with chronic myeloid leukemia, International Journal of Cancer, 1976, 18 (4): 421–31, PMID 789258, doi:10.1002/ijc.2910180405 
  5. ^ Andersson, L.C.; Nilsson, K.; Gahmberg, C.G., K562 - A human erythroleukemic cell line, International Journal of Cancer, 1979, 23 (2): 143–7, PMID 367973, doi:10.1002/ijc.2910230202 
  6. ^ Jongen-Lavrencic, M. BCR/ABL-mediated downregulation of genes implicated in cell adhesion and motility leads to impaired migration toward CCR7 ligands CCL19 and CCL21 in primary BCR/ABL-positive cells. Leukemia. 2005, 19 (3): 373–380. PMID 15674360. doi:10.1038/sj.leu.2403626. 
  7. ^ Karimiani, EG; Marriage, F; Merritt, AJ; Burthem, J; Byers, RJ; Day, PJ. Single-cell analysis of K562 cells: an imatinib-resistant subpopulation is adherent and has upregulated expression of BCR-ABL mRNA and protein.. Experimental Hematology. Mar 2014, 42 (3): 183–191.e5. PMID 24269846. doi:10.1016/j.exphem.2013.11.006. 
  8. ^ Lozzio, B.B.; Lozzio, C.B.; Bamberger, E.G.; Feliu, A.S., A multipotential leukemia cell line (K-562) of human origin, Proceedings of the Society for Experimental Biology and Medicine, 1981, 166 (4): 546–50, PMID 7194480, doi:10.3181/00379727-166-41106 
  9. ^ Lozzio, B.B.; Lozzio, C.B., Properties and usefulness of the original K-562 human myelogenous leukemia cell line, Leukemia Research, 1979, 3 (6): 363–70, PMID 95026, doi:10.1016/0145-2126(79)90033-X 
  10. ^ Britten, C.M.; Meyer, R.G.; Kreer, T.; Drexler, I.; Wölfel, T.; Herr, W., The use of HLA-A*0201-transfected K562 as standard antigen-presenting cells for CD8(+) T lymphocytes in IFN-gamma ELISPOT assays, Journal of Immunological Methods, 2002, 259 (1–2): 95–110, PMID 11730845, doi:10.1016/S0022-1759(01)00499-9 
  11. ^ Clark, R.E.; Dodi, I.A.; Hill, S.C.; Lill, J.R.; Aubert, G.; Macintyre, A.R.; Rojas, J.; Bourdon, A.; 等, Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein (PDF), Blood, 2001, 98 (10): 2887–93, PMID 11698267, doi:10.1182/blood.V98.10.2887 
  12. ^ 12.0 12.1 12.2 12.3 12.4 12.5 Duncan, Mark; DeLuca, Teresa; Kuo, Hsin-Yu; Yi, Minchang; Mrksich, Milan; Miller, William. SIRT1 is a critical regulator of K562 cell growth, survival, and differentiation. Experimental Cell Research. 2016, 344 (1): 40–52. PMC 4879089. PMID 27086164. doi:10.1016/j.yexcr.2016.04.010. 
  13. ^ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 Yang, Chunhui; Cai, Hong; Meng, Xiuxiang. Polyphyllin D induces apoptosis and differentiation in K562 human leukemia cells. Internal Immunopharmacology. 2016, 36: 17–22. PMID 27104314. doi:10.1016/j.intimp.2016.04.011. 
  14. ^ Landi, M; Catelani, G; D'Andrea, F; Ghidini, E; Amari, G; Paola, P; Bianchi, N; Gambari, R. Synthesis of glycose carbamides and evaluation of the induction of erythroid differentiation of human erythroleukemic K562 cells.. European journal of medicinal chemistry. 2009-02, 44 (2): 745–54 [2020-02-13]. PMID 18571290. doi:10.1016/j.ejmech.2008.05.001. 
  15. ^ Shimokawa, T; Nunomura, S; Fujisawa, D; Ra, C. Identification of the C/EBPα C-terminal tail residues involved in the protein interaction with GABP and their potency in myeloid differentiation of K562 cells.. Biochimica et biophysica acta. 2013-11, 1829 (11): 1207–17 [2020-02-13]. PMID 24076158. doi:10.1016/j.bbagrm.2013.09.004. 
  16. ^ Fibach, E; Bianchi, N; Borgatti, M; Prus, E; Gambari, R. Mithramycin induces fetal hemoglobin production in normal and thalassemic human erythroid precursor cells.. Blood. 2003-08-15, 102 (4): 1276–81 [2020-02-13]. PMID 12738678. doi:10.1182/blood-2002-10-3096. 
  17. ^ Zuccato, C; Bianchi, N; Borgatti, M; Lampronti, I; Massei, F; Favre, C; Gambari, R. Everolimus is a potent inducer of erythroid differentiation and gamma-globin gene expression in human erythroid cells.. Acta haematologica. 2007, 117 (3): 168–76 [2020-02-13]. PMID 17148936. doi:10.1159/000097465. 
  18. ^ 18.0 18.1 18.2 18.3 Fan, Yanhua; Lu, Hongyuan; An, Li; Wang, Changli; Zhou, Zhipeng; Feng, Fan; Ma, Hongda; Xu, Yongnan; Zhao, Qingchun. Effect of active faction of Eriocaulon sieboldianum on human leukemia K563 cells via proliferation inhibition, cell cycle arrest and apoptosis induction. Environmental Toxicology and Pharmacology. 2016, 43: 13–20. PMID 26923230. doi:10.1016/j.etap.2015.11.001. 
  19. ^ 19.0 19.1 Chylicki, K; Ehinger, M; Svedberg, H; Bergh, G; Olsson, I; Gullberg, U. p53 mediated differentiation of the erythroleukemia cell line K562. Cell Growth & Differentiation. 2000, 11 (6): 315–324. PMID 10910098. 
  20. ^ Wang, Jian; Li, Qinghua; Wang, Chijuan; Xiong, Q; Lin, Y; Sun, Q; Jin, H; Yang, F; Ren, X; Pang, T. Knock-down of CIAPIN1 sensitizes K562 chronic myeloid leukemia cells to Imatinib by regulation of cell cycle and apoptosis-associated members via NF-KB and ERK5 signaling pathway. Biochemical Pharmacology. 2016, 99: 132–145. PMID 26679828. doi:10.1016/j.bcp.2015.12.002. 

外部連結[编辑]