Volume 10, Issue 4 (Vol.10 No.4 Jan 2022)
rbmb.net 2022, 10(4): 554-564 |
Back to browse issues page
Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Abstract: (2521 Views)
Background: Acute lymphoblastic leukemia (ALL) is common in children but rare in adults. Vincristine (VCR) is one of the drugs used at the beginning of treatment. Some genes are resistant to VCR in B-ALL.
Methods: Here, we examined the effect of VCR on gene expression changes in a T-ALL cell line, Jurkat. The MTT method was used to determine the IC50 in Jurkat cells treated with different concentrations of VCR for 48 and 72 hours. Total RNA was isolated from the cells and cDNA was prepared. The Human
Cancer Drug Target PCR Array kit was used to evaluate the 84 gene expression changes in Jurkat cells. Protein-protein interaction was analyzed by STRING software.
Results: We identified 66 differentially expressed genes as comparison to untreated cells. The response to VCR-induced apoptotic events was remarkable in the pathways of heat shock protein, topoisomerase, protein kinases, cathepsins and cell cycle. In other pathways, there were resistant genes as well as sensitive genes to VCR treatment. Some proteins like HSP90AA1 and ESR1 had determining associations with other proteins.
Conclusions: The results suggest VCR target genes in T-ALL cells may be beneficial biomarkers for ALL treatment and can be used to select appropriate synergistic drugs for VCR.
Methods: Here, we examined the effect of VCR on gene expression changes in a T-ALL cell line, Jurkat. The MTT method was used to determine the IC50 in Jurkat cells treated with different concentrations of VCR for 48 and 72 hours. Total RNA was isolated from the cells and cDNA was prepared. The Human
Cancer Drug Target PCR Array kit was used to evaluate the 84 gene expression changes in Jurkat cells. Protein-protein interaction was analyzed by STRING software.
Results: We identified 66 differentially expressed genes as comparison to untreated cells. The response to VCR-induced apoptotic events was remarkable in the pathways of heat shock protein, topoisomerase, protein kinases, cathepsins and cell cycle. In other pathways, there were resistant genes as well as sensitive genes to VCR treatment. Some proteins like HSP90AA1 and ESR1 had determining associations with other proteins.
Conclusions: The results suggest VCR target genes in T-ALL cells may be beneficial biomarkers for ALL treatment and can be used to select appropriate synergistic drugs for VCR.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2021/08/13 | Accepted: 2021/08/25 | Published: 2022/02/7
Received: 2021/08/13 | Accepted: 2021/08/25 | Published: 2022/02/7
References
1. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7(6): e577. [DOI:10.1038/bcj.2017.53] [PMID] [PMCID]
2. Pulte D, Jansen L, Gondos A, Katalinic A, Barnes B, Ressing M, et al. Survival of adults with acute lymphoblastic leukemia in Germany and the United States. PLOS ONE. 2014;9(1):e85554. [DOI:10.1371/journal.pone.0085554] [PMID] [PMCID]
3. Samuels AL, Beesley AH, Yadav BD, Papa RA, Sutton R, Anderson D, et al. A pre-clinical model of resistance to induction therapy in pediatric acute lymphoblastic leukemia. Blood Cancer J. 2014;4(8): e232. [DOI:10.1038/bcj.2014.52] [PMID] [PMCID]
4. Holleman A, Cheok MH, Boer MLD, Yang W, Veerman AJP, Kazemier KM, et al. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. N Engl J Med. 2004;351(6):533-42. [DOI:10.1056/NEJMoa033513] [PMID]
5. Lugthart S, Cheok MH, Den Boer ML, Yang W, Holleman A, Cheng C, et al. Identification of genes associated with chemo-therapy cross-resistance and treatment response in childhood acute lymphoblastic leukemia. Cancer Cell. 2005;7(4):375-86. [DOI:10.1016/j.ccr.2005.03.002] [PMID]
6. Szczepanek J, Pogorzala M, Jarzab M, Oczko-Wojciechowska M, Kowalska M, Tretyn A. Expression profiles of signal transduction genes in ex vivo drug-resistant pediatric acute lymphoblastic leukemia. Anticancer Res. 2012;32(2):503-6.
7. Groninger E, Meeuwsen-De Boar T, Koopmans P, Uges D, Sluiter W, Veerman A, et al. Pharmacokinetics of vincristine monotherapy in childhood acute lymphoblastic leukemia. Pediatr Res. 2002;52(1):113-8. [DOI:10.1203/00006450-200207000-00021] [PMID]
8. Gonzalez-Cid M, Cuello MT, Larripa I. Comparison of the aneugenic effect of vinorelbine and vincristine in cultured human lymphocytes. Mutagenesis 1999;14(1):63-66. [DOI:10.1093/mutage/14.1.63] [PMID]
9. Ceppi F, Langlois-Pelletier C, Gagné V, Rousseau J, Ciolino C, De Lorenzo S, et al. Polymorphisms of the vincristine pathway and response to treatment in children with childhood acute lymphoblastic leukemia. Pharmacogenomics. 2014;15(8):1105-1116. [DOI:10.2217/pgs.14.68] [PMID] [PMCID]
10. Groninger E, Meeuwsen-De Boer GJ, De Graaf SSN, Kamps WA, De Bont ESJM. Vincristine induced apoptosis in acute lymphoblastic leukemia cells: a mitochondrial controlled pathway regulated by reactive oxygen species?. Int J Oncol. 2002;21(6):1339-45. [DOI:10.3892/ijo.21.6.1339] [PMID]
11. Beesley AH, Firth MJ, Anderson D, Samuels AL, Ford J, Kees UR. Drug-Gene Modeling in Pediatric T-Cell Acute Lymphoblastic Leukemia Highlights Importance of 6-Mercaptopurine for Outcome. Cancer Res. 2013;73(9):2749-59. [DOI:10.1158/0008-5472.CAN-12-3852] [PMID]
12. Looi CY, Arya A, Cheah FK, Muharram B, Leong KH, Mohamad K, et al. Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum (L.) seeds. PLOS ONE. 2013;8(2):e56643. [DOI:10.1371/journal.pone.0056643] [PMID] [PMCID]
13. Aleem E, Arceci RJ. Targeting cell cycle regulators in hematologic malignancies. Front Cell Dev Biol. 2015;3:16. [DOI:10.3389/fcell.2015.00016] [PMID] [PMCID]
14. Mancini F, Teveroni E, Conza GD, Monteleone V, Arisi I, Pellegrino M, et al. MDM4 actively restrains cytoplasmic mTORC1 by sensing nutrient availability. Mol Cancer. 2017;16(1):55. [DOI:10.1186/s12943-017-0626-7] [PMID] [PMCID]
15. Sheng X, Tong N, Tao G, Luo D, Wang M, Fang Y, et al. TERT polymorphisms modify the risk of acute lymphoblastic leukemia in Chinese children. Carcinogenesis. 2013;34(1):228-235. [DOI:10.1093/carcin/bgs325] [PMID]
16. Turk V, Stoka V, Vasiljeva O, Renko M, Sun T, Turk B, et al. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 2012;1824(1):68-88. [DOI:10.1016/j.bbapap.2011.10.002] [PMID] [PMCID]
17. Li TK, Liu LF. Tumor cell death induced by topoisomerase-targeting druges. Annual Review of Pharmacology and Toxicology. 2001; 41:53-77. [DOI:10.1146/annurev.pharmtox.41.1.53] [PMID]
18. Redell MS, Tweardy DJ. Targeting transcription factors in cancer: Challenges and evolving strategies. Drug Discov Today Technol. 2006;3(3):261-7. [DOI:10.1016/j.ddtec.2006.09.010] [PMID]
19. Lopez-Bergami P, Lau E, Ronai Z. Emerging roles of ATF2 and the dynamic AP1 network in cancer. Nature Reviews Cancer. 2010;10(1):65-76. [DOI:10.1038/nrc2681] [PMID] [PMCID]
20. Thomas X, Campos L, Le QH, Guyotat D. Heat shock proteins and acute leukemias. Hematology. 2005;10(3):225-35. [DOI:10.1080/10245330500093120] [PMID]
21. Verza FA, Das U, AL, Dimmock JR, Marins M. Roles of histone deacetylases and inhibitors in anticancer therapy. Cancers (Basel). 2020;12(6):1664. [DOI:10.3390/cancers12061664] [PMID] [PMCID]
22. Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci. 2009;122(Pt 20):3589-94. [DOI:10.1242/jcs.051011] [PMID] [PMCID]
23. Liang X, Xin X, Qi D, Fu C, Ding M. Silencing the PIK3CA gene enhances the sensitivity of childhood leukemia cells to chemotherapy drugs by suppressing the phosphorylation of Akt. Yonsei Med J. 2019;60(2):182-190. [DOI:10.3349/ymj.2019.60.2.182] [PMID] [PMCID]
24. Bartram I, Erben U, Ortiz-Tanchez J, Blunert K, Schlee C, Neumann M, et al. Inhibition of IGF1-R overcomes IGFBP7-induced chemotherapy resistance in T-ALL. BMC Cancer. 2015;15:663. [DOI:10.1186/s12885-015-1677-z] [PMID] [PMCID]
25. Abbaspour Babaei M, Kamalidehghan B, Saleem M, Huri HZ, Ahmadipour F. Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells. Drug Des Devel Ther. 2016;10:2443-59. [DOI:10.2147/DDDT.S89114] [PMID] [PMCID]
26. Hameda NAM, Ghallaba O, El-Neilyb D. Glutathione-S-transferase P1 as a risk factor for Egyptian patients with chronic myeloid leukemia. The Egyptian Journal of Haematology. 2016;41(2):65-69. [DOI:10.4103/1110-1067.186408]
27. Steinbach D, Legrand O. ABC transporters and drug resistance in leukemia: was P-gp nothing but the first head of the Hydra?. Leukemia. 2007;21:1172-6. [DOI:10.1038/sj.leu.2404692] [PMID]
28. Lei J, Li Q, Gao Y, Zhao L, Liu Y. Increased PKCα activity by Rak1 overexpression is responsible for chemotherapy resistance in T-cell acute lymphoblastic leukemia-derived cell line. Sci Rep. 2016;6:33717. [DOI:10.1038/srep33717] [PMID] [PMCID]
29. Hartsink-Segers SA, Zwaan CM, Exalto C, Luijendijk MWJ, Calvert VS, Petricoin EF, et al. Aurora kinases in childhood acute leukemia: the promise of aurora B as therapeutic target. Leukemia. 2013;27(3):560-568. [DOI:10.1038/leu.2012.256] [PMID] [PMCID]
30. Renner AG, Santos CD, Recher C, Bailly C, Creancier L, Kruczynski A, et al. Polo-like kinase1 is overexpressed in acute myeloid leukemia and its inhibition preferentially targets the proliferation of leukemic cells. Blood. 2009;114(3):659-62. [DOI:10.1182/blood-2008-12-195867] [PMID]
31. Yakimchuk K, Iravani M, Hasni MS, Rhönnstad P, Nilsson S, Jondal M, et al. Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo. Leukemia. 2011;25(7):1103-10. [DOI:10.1038/leu.2011.68] [PMID]
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |