Abstract
Cancer of blood or bone marrow-derived cells dysregulates normal hematopoiesis and accounts for over 6% of all cancer cases annually. Proteomic analyses of blood cancers have improved our understanding of disease mechanisms and identified numerous proteins of clinical relevance. For many years, gel-based proteomic studies have aided in the discovery of novel diagnostic, prognostic, and predictive biomarkers, as well as therapeutic targets, in various diseases, including blood cancer. Fluorescence two-dimensional difference gel electrophoresis (2D-DIGE) facilitates comparative proteomic research to identify differential protein expression in a simple and reproducible manner. The versatility of 2D-DIGE as a quantitative proteomic technique has provided insight into various aspects of blood cancer pathology, including disease development, prognostic subtypes, and drug resistance. The ability to couple 2D-DIGE with additional downstream mass spectrometry-based techniques yields comprehensive workflows capable of identifying proteins of biological and clinical significance. The application of 2D-DIGE in blood cancer research has significantly contributed to the increasingly important initiative of precision medicine. This chapter will focus on the influential role of 2D-DIGE as a tool in blood cancer research.
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References
Sung H, Ferlay J, Siegel RL et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660
Hao T, Li-Talley M, Buck A, Chen W (2019) An emerging trend of rapid increase of leukemia but not all cancers in the aging population in the United States. Sci Rep 9:12070. https://doi.org/10.1038/s41598-019-48445-1
Hochhaus A, Larson RA, Guilhot F et al (2017) Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med 376:917–927. https://doi.org/10.1056/NEJMoa1609324
Pulte D, Jansen L, Brenner H (2020) Changes in long term survival after diagnosis with common hematologic malignancies in the early 21st century. Blood Cancer J 10:56. https://doi.org/10.1038/s41408-020-0323-4
Schlegelberger B, Mecucci C, Wlodarski M (2021) Review of guidelines for the identification and clinical care of patients with genetic predisposition for hematological malignancies. Familial Cancer 20:295–303. https://doi.org/10.1007/s10689-021-00263-z
Marcus K, Lelong C, Rabilloud T (2020) What room for two-dimensional gel-based proteomics in a shotgun proteomics world? Proteomes 8:17. https://doi.org/10.3390/proteomes8030017
Fu Y, Zhang Y, Khoo BL (2021) Liquid biopsy technologies for hematological diseases. Med Res Rev 41:246–274. https://doi.org/10.1002/med.21731
Ummanni R, Mundt F, Pospisil H et al (2011) Identification of clinically relevant protein targets in prostate cancer with 2D-DIGE coupled mass spectrometry and systems biology network platform. PLoS One 6:e16833. https://doi.org/10.1371/journal.pone.0016833
Reddy KRK, Dasari C, Duscharla D et al (2018) Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is frequently upregulated in prostate cancer, and its overexpression conveys tumor growth and angiogenesis by metabolizing asymmetric dimethylarginine (ADMA). Angiogenesis 21:79–94. https://doi.org/10.1007/s10456-017-9587-0
Kami Reddy KR, Dasari C, Vandavasi S et al (2019) Novel cellularly active inhibitor regresses DDAH1 induced prostate tumor growth by restraining tumor angiogenesis through targeting DDAH1/ADMA/NOS pathway. ACS Comb Sci 21:241–256. https://doi.org/10.1021/acscombsci.8b00133
Forthun RB, Aasebø E, Rasinger JD et al (2018) Phosphoprotein DIGE profiles reflect blast differentiation, cytogenetic risk stratification, FLT3/NPM1 mutations and therapy response in acute myeloid leukaemia. J Proteome 173:32–41. https://doi.org/10.1016/j.jprot.2017.11.014
Hu J, Lin M, Liu T et al (2011) DIGE-based proteomic analysis identifies nucleophosmin/B23 and nucleolin C23 as over-expressed proteins in relapsed/refractory acute leukemia. Leuk Res 35:1087–1092. https://doi.org/10.1016/j.leukres.2011.01.010
Ma T-Z, Piao Z, Jin S-Y, Kwak Y-G (2019) Differential expression of serum proteins in multiple myeloma. Exp Ther Med 17:649–656. https://doi.org/10.3892/etm.2018.7010
Saha S, Banerjee S, Banerjee D et al (2014) 2DGE and DIGE based proteomic study of malignant B-cells in B-cell acute lymphoblastic leukemia. EuPA Open Proteom 3:13–26. https://doi.org/10.1016/j.euprot.2014.01.002
Podar K, Leleu X (2021) Relapsed/refractory multiple myeloma in 2020/2021 and beyond. Cancers 13:5154. https://doi.org/10.3390/cancers13205154
Rajpal R, Dowling P, Meiller J et al (2011) A novel panel of protein biomarkers for predicting response to thalidomide-based therapy in newly diagnosed multiple myeloma patients. Proteomics 11:1391–1402. https://doi.org/10.1002/pmic.201000471
Chanukuppa V, Taware R, Taunk K et al (2021) Proteomic alterations in multiple myeloma: a comprehensive study using bone marrow interstitial fluid and serum samples. Front Oncol 10:566804
Kantarjian HM, Keating MJ, Freireich EJ (2018) Toward the potential cure of leukemias in the next decade. Cancer 124:4301–4313. https://doi.org/10.1002/cncr.31669
Forthun RB, Hellesøy M, Sulen A et al (2019) Modulation of phospho-proteins by interferon-alpha and valproic acid in acute myeloid leukemia. J Cancer Res Clin Oncol 145:1729–1749. https://doi.org/10.1007/s00432-019-02931-1
Gan D, Chen Y, Wu Z et al (2021) Doxorubicin/nucleophosmin binding protein-conjugated nanoparticle enhances anti-leukemia activity in acute lymphoblastic leukemia cells in vitro and in vivo. Front Pharmacol 12:607755. https://doi.org/10.3389/fphar.2021.607755
Mugnaini EN, Ghosh N (2016) Lymphoma. Prim Care 43:661–675. https://doi.org/10.1016/j.pop.2016.07.012
Kj S, Jh P, Hj I, Sd A (2020) Survival and long-term toxicities of pediatric Hodgkin lymphoma after combined modality treatment: a single institute experience. Radiat Oncol J 38:198–206. https://doi.org/10.3857/roj.2020.00346
Yeh JM, Diller L (2012) Pediatric Hodgkin lymphoma: trade-offs between short- and long-term mortality risks. Blood 120:2195–2202. https://doi.org/10.1182/blood-2012-02-409821
Repetto O, Mussolin L, Elia C et al (2018) Proteomic identification of plasma biomarkers in children and adolescents with recurrent Hodgkin lymphoma. J Cancer 9:4650–4658. https://doi.org/10.7150/jca.27560
Repetto O, Lovisa F, Elia C et al (2021) Proteomic exploration of plasma exosomes and other small extracellular vesicles in pediatric Hodgkin lymphoma: a potential source of biomarkers for relapse occurrence. Diagnostics 11:917. https://doi.org/10.3390/diagnostics11060917
Fujii K, Suzuki N, Ikeda K et al (2012) Proteomic study identified HSP 70kDa protein 1A as a possible therapeutic target, in combination with histone deacetylase inhibitors, for lymphoid neoplasms. J Proteome 75:1401–1410. https://doi.org/10.1016/j.jprot.2011.11.010
Fujii K, Idogawa M, Suzuki N et al (2021) Functional depletion of HSP72 by siRNA and quercetin enhances vorinostat-induced apoptosis in an HSP72-overexpressing cutaneous T-cell lymphoma cell line, Hut78. Int J Mol Sci 22:11258. https://doi.org/10.3390/ijms222011258
Acknowledgment
Research in the author’s laboratory has been supported by the Kathleen Lonsdale Institute for Human Health Research, Maynooth University.
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Dunphy, K., Dowling, P. (2023). DIGE-Based Biomarker Discovery in Blood Cancers. In: Ohlendieck, K. (eds) Difference Gel Electrophoresis. Methods in Molecular Biology, vol 2596. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2831-7_8
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DOI: https://doi.org/10.1007/978-1-0716-2831-7_8
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