Skip to main content
NCBI home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2018 Aug 18;165(4):530–543. doi: 10.1007/s10517-018-4210-y

Proteomic Profiling of HL-60 Cells during ATRA-Induced Differentiation

I V Vakhrushev 1,✉, S E Novikova 1, A V Tsvetkova 1, P A Karalkin 1, M A Pyatnitskii 1, V G Zgoda 1, K N Yarygin 1
PMCID: PMC7087771  PMID: 30121918

Abstract

Acute promyelocytic leukemia, a form of acute myeloid leukemia, is characterized by cell differentiation arrest at the promyelocyte stage. Current therapeutic options include administration of all trans-retinoic acid (ATRA), but this treatment produces many side effects. ATRA is known to induce differentiation of leukemic cells into granulocytes, but the mechanism of this process is poorly studied. We performed comparative proteomic profiling of HL-60 promyelocytic cells at different stages of ATRA-induced differentiation to identify differentially expressed proteins by high-resolution mass spectrometry and relative quantitative analysis without isotope labels. A total of 1162 proteins identified by at least two unique peptides were analyzed, among them 46 and 172 differentially expressed proteins were identified in the nuclear and cytosol fractions, respectively. These differentially expressed proteins can represent candidate targets for combination therapy of acute promyelocytic leukemia.

Key Words: acute promyelocytic leukemia, trans-retinoic acid, targeted therapy

Footnotes

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 71-85, June, 2018

References

  • 1.Álvarez-Chaver P, De Chiara L, Martínez-Zorzano VS. Proteomic profiling for colorectal cancer biomarker discovery. Methods Mol. Biol. 2018;1765:241-269. [DOI] [PubMed]
  • 2.Birnie GD. The HL60 cell line: a model system for studying human myeloid cell differentiation. Br. J. Cancer Suppl. 1988;9:41–45. [PMC free article] [PubMed] [Google Scholar]
  • 3.Concolino A, Olivo E, Tammè L, Fiumara CV, De Angelis MT, Quaresima B, Agosti V, Costanzo FS, Cuda G, Scumaci D. Proteomics analysis to assess the role of mitochondria in BRCA1-mediated breast tumorigenesis. Proteomes. 2018;6(2). pii: E16. doi: 10.3390/proteomes6020016. [DOI] [PMC free article] [PubMed]
  • 4.Coombs CC, Tavakkoli M, Tallman MS. Acute promyelocytic leukemia: where did we start, where are we now, and the future. Blood Cancer J. 2015;5:e304. doi: 10.1038/bcj.2015.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Cox J, Hein MY, Luber CA, Paron I, Nagaraj N, Mann M. Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ. Mol. Cell. Proteomics. 2014;13(9):2513–2526. doi: 10.1074/mcp.M113.031591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Dixon RA, Diehl RE, Opas E, Rands E, Vickers PJ, Evans JF, Gillard JW, Miller DK. Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis. Nature. 1990;343:282–284. doi: 10.1038/343282a0. [DOI] [PubMed] [Google Scholar]
  • 7.Hong C, An S, Son M, Hong SS, Lee DH, Lee C. In-vitro cell tests using doxorubicin-loaded polymeric TiO2 nanotubes used for cancer photothermotherapy. Anticancer Drugs. 2012;23(5):553–560. doi: 10.1097/CAD.0b013e328350446b. [DOI] [PubMed] [Google Scholar]
  • 8.Huang H, Qin Y, Xu R, You X, Teng R, Yang L, Xu M, Liu H. Combination therapy with arsenic trioxide, all-trans retinoic acid, and chemotherapy in acute promyelocytic leukemia patients with various relapse risks. Leuk. Res. 2012;36(7):841–845. doi: 10.1016/j.leukres.2012.03.027. [DOI] [PubMed] [Google Scholar]
  • 9.Huang J, Casas Garcia GP, Perugini MA, Fox A, Bond C, Lee M. Crystal structure of a SFPQ/PSPC1 heterodimer provides insights into preferential heterodimerization of human DBHS family proteins. J. Biol. Chem. 2018. Mar 12. pii: jbc. RA117.001451. doi: 10.1074/jbc.RA117.001451. [DOI] [PMC free article] [PubMed]
  • 10.Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, Browett P, Grigg A, Firkin F, Hugman A, Reynolds J, Di Iulio J, Tiley C, Taylor K, Filshie R, Seldon M, Taper J, Szer J, Moore J, Bashford J, Seymour JF Australasian Leukaemia and Lymphoma Group. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4) Blood. 2012;120(8):1570–1580. doi: 10.1182/blood-2012-02-410746. [DOI] [PubMed] [Google Scholar]
  • 11.Li T, Ma R, Zhang Y, Mo H, Yang X, Hu S, Wang L, Nova-kovic VA, Chen H, Kou J, Bi Y, Yu B, Fang S, Wang J, Zhou J, Shi J. Arsenic trioxide promoting ETosis in acute promyelocytic leukemia through mTOR-regulated autophagy. Cell Death Dis. 2018;9(2):75. doi: 10.1038/s41419-017-0018-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Reyes-Sebastian J, Montiel-Cervantes LA, Reyes-Maldonado E, Dominguez-Lopez ML, Ortiz-Butron R, Castillo-Alvarez A, Lezama RA. Cell proliferation and inhibition of apoptosis are related to c-Kit activation in leukaemic lymphoblasts. Hematology. 2018;Mar 1:1-10. doi: 10.1080/10245332.2018.1444564. [DOI] [PubMed]
  • 13.Rothofsky ML, Lin SL. CROC-1 encodes a protein which mediates transcriptional activation of the human FOS promoter. Gene. 1997;195(2):141–149. doi: 10.1016/S0378-1119(97)00097-8. [DOI] [PubMed] [Google Scholar]
  • 14.Shi Y, Xu X, Zhang Q, Fu G, Mo Z, Wang GS, Kishi S, Yang XL. tRNA synthetase counteracts c-Myc to develop functional vasculature. Elife. 2014;3:e02349. doi: 10.7554/eLife.02349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Sewer MB, Nguyen VQ, Huang CJ, Tucker PW, Kagawa N, Waterman MR. Transcriptional activation of human CYP17 in H295R adrenocortical cells depends on complex formation among p54(nrb)/NonO, protein-associated splicing factor, and SF-1, a complex that also participates in repression of transcription. Endocrinology. 2002;143(4):1280–1290. doi: 10.1210/endo.143.4.8748. [DOI] [PubMed] [Google Scholar]
  • 16.Simicevic J, Schmid AW, Gilardoni PA, Zoller B, Raghav SK, Krier I, Gubelmann C, Lisacek F, Naef F, Moniatte M, Deplancke B. Absolute quantification of transcription factors during cellular differentiation using multiplexed targeted proteomics. Nat. Methods. 2013;10(6):570–576. doi: 10.1038/nmeth.2441. [DOI] [PubMed] [Google Scholar]
  • 17.Takahashi H, Hatta Y, Iriyama N, Hasegawa Y, Uchida H, Nakagawa M, Makishima M, Takeuchi J, Takei M. Induced differentiation of human myeloid leukemia cells into M2 macrophages by combined treatment with retinoic acid and 1alpha,25-dihydroxyvitamin D3. PLoS One. 2014;9(11):e113722. doi: 10.1371/journal.pone.0113722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Tasseff R, Jensen HA, Congleton J, Dai D, Rogers KV, Sagar A, Bunaciu RP, Yen A, Varner JD. An effective model of the retinoic acid induced HL-60 differentiation program. Sci. Rep. 2017;7(1):14327. doi: 10.1038/s41598-017-14523-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Tong X, Drapkin R, Yalamanchili R, Mosialos G, Kieff E. The Epstein-Barr virus nuclear protein 2 acidic domain forms a complex with a novel cellular coactivator that can interact with TFIIE. Mol. Cell. Biol. 1995;15(9):4735–4744. doi: 10.1128/MCB.15.9.4735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Van Damme J, Rampart M, Conings R, Decock B, Van Osselaer N, Willems J, Billiau A. The neutrophil-activating proteins interleukin 8 and beta-thromboglobulin: in vitro and in vivo comparison of NH2-terminally processed forms. Eur. J. Immunol. 1990;20(9):2113–2118. doi: 10.1002/eji.1830200933. [DOI] [PubMed] [Google Scholar]
  • 21.Valenzuela SM, Mazzanti M, Tonini R, Qiu MR, Warton K, Musgrove EA, Campbell TJ, Breit SN. The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle. J. Physiol. 2000;529(Pt 3):541–552. doi: 10.1111/j.1469-7793.2000.00541.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Vaquerizas JM, Kummerfeld SK, Teichmann SA. Luscombe NM. A census of human transcription factors: function, expression and evolution. Nat. Rev. Genet. 2009;10(4):252–263. doi: 10.1038/nrg2538. [DOI] [PubMed] [Google Scholar]
  • 23.Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008;111(5):2505–2515. doi: 10.1182/blood-2007-07-102798. [DOI] [PubMed] [Google Scholar]
  • 24.Wiśniewski JR, Zougman A, Nagaraj N, Mann M. Universal sample preparation method for proteome analysis. Nat. Methods. 2009;6(5):359–362. doi: 10.1038/nmeth.1322. [DOI] [PubMed] [Google Scholar]
  • 25.Yao YL, Yang WM. Nuclear proteins: promising targets for cancer drugs. Curr. Cancer Drug Targets. 2005;5(8):595–610. doi: 10.2174/156800905774932815. [DOI] [PubMed] [Google Scholar]
  • 26.Zhang C, Leng W, Sun C, Lu T, Chen Z, Men X, Wang Y, Wang G, Zhen B, Qin J. Urine proteome profiling predicts lung cancer from control cases and other tumors. EBioMedicine. 2018. Mar 17. pii: S2352-3964(18)30093-8. doi: 10.1016/j.ebiom.2018.03.009. [DOI] [PMC free article] [PubMed]
  • 27.Zhang Z, Miao L, Xin X, Zhang J, Yang S, Miao M, Kong X, Jiao B. Underexpressed CNDP2 participates in gastric cancer growth inhibition through activating the MAPK signaling pathway. Mol. Med. 2014;20:17–28. doi: 10.2119/molmed.2013.00102. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Bulletin of Experimental Biology and Medicine are provided here courtesy of Nature Publishing Group

RESOURCES