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.
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Álvarez-Chaver P, De Chiara L, Martínez-Zorzano VS. Proteomic profiling for colorectal cancer biomarker discovery. Methods Mol. Biol. 2018;1765:241-269.
Birnie GD. The HL60 cell line: a model system for studying human myeloid cell differentiation. Br. J. Cancer Suppl. 1988;9:41-45.
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: https://doi.org/10.3390/proteomes6020016.
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: https://doi.org/10.1038/bcj.2015.25.
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.
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.
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.
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.
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: https://doi.org/10.1074/jbc.RA117.001451.
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; quiz 1752.
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: https://doi.org/10.1038/s41419-017-0018-3.
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: https://doi.org/10.1080/10245332.2018.1444564.
Rothofsky ML, Lin SL. CROC-1 encodes a protein which mediates transcriptional activation of the human FOS promoter. Gene. 1997;195(2):141-149.
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: https://doi.org/10.7554/eLife.02349.
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.
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.
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:https://doi.org/10.1371/journal.pone.0113722.
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: https://doi.org/10.1038/s41598-017-14523-5.
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.
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.
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.
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.
Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008;111(5):2505-2515.
Wiśniewski JR, Zougman A, Nagaraj N, Mann M. Universal sample preparation method for proteome analysis. Nat. Methods. 2009;6(5):359-362.
Yao YL, Yang WM. Nuclear proteins: promising targets for cancer drugs. Curr. Cancer Drug Targets. 2005;5(8):595-610.
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: https://doi.org/10.1016/j.ebiom.2018.03.009.
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.
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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 71-85, June, 2018
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Vakhrushev, I.V., Novikova, S.E., Tsvetkova, A.V. et al. Proteomic Profiling of HL-60 Cells during ATRA-Induced Differentiation. Bull Exp Biol Med 165, 530–543 (2018). https://doi.org/10.1007/s10517-018-4210-y
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DOI: https://doi.org/10.1007/s10517-018-4210-y