Aberrant DNA methylation of key genes and Acute Lymphoblastic Leukemia

Biomedicine and Pharmacotherapy

Volumn 97, Issue , 2018, Pages 1493-1500

  Rahmani, Mina ^a,b   Talebi, Mehdi ^c   Hagh, Majid Farshdousti ^c,d   Feizi, Abbas A Hosseinpour ^c   Solali, Saeed ^a,e  

^a TABRIZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b TABRIZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^c TABRIZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^d TABRIZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^e TABRIZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

Acute lymphoblastic leukemia; DNA methyltransferase; Epigenetic mechanism; Gene regulation; Methylation

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 1C; CYCLIN DEPENDENT KINASE INHIBITOR 2B; CYTOCHROME P450 1B1; PROTEIN TYROSINE PHOSPHATASE SHP 1; SPALT LIKE TRANSCRIPTION FACTOR 4; TRANSCRIPTION FACTOR; TUMOR PROTEIN P73; UNCLASSIFIED DRUG;

ACUTE LYMPHOBLASTIC LEUKEMIA; CELL CYCLE REGULATION; CHRONIC MYELOID LEUKEMIA; DNA METHYLATION; DOWN REGULATION; EPIGENETICS; GENE INACTIVATION; HUMAN; LYMPHOCYTE PROLIFERATION; PATHOGENESIS; PRIORITY JOURNAL; PROMOTER REGION; REVIEW; TUMOR GROWTH; TUMOR SUPPRESSOR GENE; BIOLOGICAL MODEL; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; TUMOR GENE;

DNA METHYLATION; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, LEUKEMIC; GENES, NEOPLASM; HUMANS; MODELS, BIOLOGICAL; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA;

EID: 85034448227     PISSN: 07533322     EISSN: 19506007     Source Type: Journal    
DOI: 10.1016/j.biopha.2017.11.033     Document Type: Review

References (111)

1. Guillamot, M., Cimmino, L., Aifantis, I., The impact of DNA methylation in hematopoietic malignancies. Trends Cancer 2:2 (2016), 70–83.
2. Pui, C.-H., Robison, L.L., Look, A.T., Acute lymphoblastic leukaemia. Lancet 371:9617 (2008), 1030–1043.
3. Asai, D., Imamura, T., Suenobu, Si., Saito, A., Hasegawa, D., Deguchi, T., Hashii, Y., Matsumoto, K., Kawasaki, H., Hori, H., IKZF1 deletion is associated with a poor outcome in pediatric B‐cell precursor acute lymphoblastic leukemia in Japan. Cancer Med. 2:3 (2013), 412–419.
4. Nikbakht, M., Study of aberrant promoter hypermethylation of multiple tumor suppressor genes in childhood acute lymphoblastic leukemia ALL potential diagnostic significance. 2016.
5. Tao, S., Wang, C., Chen, Y., Deng, Y., Zhou, L., Zhang, X., He, Z., Yu, L., Btk and NFκB as prognostic biomarkers and potential therapeutic targets in B cell acute lymphoblastic leukemia. Int. J. Clin. Exp. Pathol. 9:8 (2016), 7995–8005.
6. Einav Nili, G.-Y., Saito, Y., Egger, G., Jones, P.A., Cancer epigenetics: modifications, screening, and therapy. Annu. Rev. Med. 59 (2008), 267–280.
7. Mullighan, C.G., Miller, C.B., Radtke, I., Phillips, L.A., Dalton, J., Ma, J., White, D., Hughes, T.P., Le Beau, M.M., Pui, C.-H., BCR–ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature 453:7191 (2008), 110–114.
8. Mullighan, C.G., Zhang, J., Harvey, R.C., Collins-Underwood, J.R., Schulman, B.A., Phillips, L.A., Tasian, S.K., Loh, M.L., Su, X., Liu, W., JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. 106:23 (2009), 9414–9418.
9. Mullighan, C.G., Collins-Underwood, J.R., Phillips, L.A., Loudin, M.G., Liu, W., Zhang, J., Ma, J., Coustan-Smith, E., Harvey, R.C., Willman, C.L., Rearrangement of CRLF2 in B-progenitor–and Down syndrome–associated acute lymphoblastic leukemia. Nat. Genet. 41:11 (2009), 1243–1246.
10. Cario, G., Zimmermann, M., Romey, R., Gesk, S., Vater, I., Harbott, J., Schrauder, A., Moericke, A., Izraeli, S., Akasaka, T., Presence of the P2RY8-CRLF2 rearrangement is associated with a poor prognosis in non–high-risk precursor B-cell acute lymphoblastic leukemia in children treated according to the ALL-BFM 2000 protocol. Blood 115:26 (2010), 5393–5397.
11. Hertzberg, L., Vendramini, E., Ganmore, I., Cazzaniga, G., Schmitz, M., Chalker, J., Shiloh, R., Iacobucci, I., Shochat, C., Zeligson, S., Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. Blood 115:5 (2010), 1006–1017.
12. Milani, L., Lundmark, A., Kiialainen, A., Nordlund, J., Flaegstad, T., Forestier, E., Heyman, M., Jonmundsson, G., Kanerva, J., Schmiegelow, K., DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia. Blood 115:6 (2010), 1214–1225.
13. Florean, C., Schnekenburger, M., Grandjenette, C., Dicato, M., Diederich, M., Epigenomics of leukemia: from mechanisms to therapeutic applications. Epigenomics 3:5 (2011), 581–609.
14. Figueroa, M.E., Reimers, M., Thompson, R.F., Ye, K., Li, Y., Selzer, R.R., Fridriksson, J., Paietta, E., Wiernik, P., Green, R.D., An integrative genomic and epigenomic approach for the study of transcriptional regulation. PloS One, 3(3), 2008, e1882.
15. Singal, R., Ginder, G.D., DNA methylation. Blood 93:12 (1999), 4059–4070.
16. Jones, P.A., Baylin, S.B., The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 3:6 (2002), 415–428.
17. Bootwala, Y., Bandyopadhyay, D., Epigenetic therapies of cancer. Curr. Cancer Ther. Rev. 2:2 (2006), 127–135.
18. Baylin, S.B., DNA methylation and gene silencing in cancer. Nat. Rev. Clin. Oncol., 2(S1), 2005, S4.
19. Deaton, A.M., Bird, A., CpG islands and the regulation of transcription. Genes Dev. 25:10 (2011), 1010–1022.
20. Okada, Y., Feng, Q., Lin, Y., Jiang, Q., Li, Y., Coffield, V.M., Su, L., Xu, G., Zhang, Y., hDOT1L links histone methylation to leukemogenesis. Cell 121:2 (2005), 167–178.
21. Figueroa, M.E., Chen, S.-C., Andersson, A.K., Phillips, L.A., Li, Y., Sotzen, J., Kundu, M., Downing, J.R., Melnick, A., Mullighan, C.G., Integrated genetic and epigenetic analysis of childhood acute lymphoblastic leukemia. J. Clin. Investig. 123:7 (2013), 3099–3111.
22. Nordlund, J., Bäcklin, C.L., Wahlberg, P., Busche, S., Berglund, E.C., Eloranta, M.-L., Flaegstad, T., Forestier, E., Frost, B.-M., Harila-Saari, A., Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia. Genome Biol., 14(9), 2013, r105.
23. Jeong, M., Goodell, M.A., New answers to old questions from genome-wide maps of DNA methylation in hematopoietic cells. Exp. Hematol. 42:8 (2014), 609–617.
24. Bahari, G., Hashemi, M., Naderi, M., Taheri, M., TET2 Promoter DNA Methylation and Expression in Childhood Acute Lymphoblastic Leukemia. Asian Pacif. J. Cancer Prev., 17(8), 2016, 3959.
25. Portha, B., Fournier, A., Kioon, M.A., Mezger, V., Movassat, J., Early environmental factors, alteration of epigenetic marks and metabolic disease susceptibility. Biochimie 97 (2014), 1–15.
26. Shen, L., Waterland, R.A., Methods of DNA methylation analysis. Curr. Opin. Clin. Nutr. Metab. Care 10:5 (2007), 576–581.
27. Wojdacz, T.K., Dobrovic, A., Methylation-sensitive high resolution melting (MS-HRM): a new approach for sensitive and high-throughput assessment of methylation. Nucleic Acids Res., 35(6), 2007, e41.
28. Herman, J.G., Graff, J.R., Myöhänen, S., Nelkin, B.D., Baylin, S.B., Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc. Natl. Acad. Sci. 93:18 (1996), 9821–9826.
29. Gómez-del Arco, P., Maki, K., Georgopoulos, K., Phosphorylation controls Ikaros's ability to negatively regulate the G1-S transition. Mol. Cell. Biol. 24:7 (2004), 2797–2807.
30. Kastner, P., Dupuis, A., Gaub, M.-P., Herbrecht, R., Lutz, P., Chan, S., Function of Ikaros as a tumor suppressor in B cell acute lymphoblastic leukemia. Am. J. Blood Res. 3:1 (2013), 1–13.
31. Sun, L., Heerema, N., Crotty, L., Wu, X., Navara, C., Vassilev, A., Sensel, M., Reaman, G.H., Uckun, F.M., Expression of dominant-negative and mutant isoforms of the antileukemic transcription factor Ikaros in infant acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. 96:2 (1999), 680–685.
32. Liu, M., Ge, Y., Payton, S.G., Aboukameel, A., Buck, S., Flatley, R.M., Haska, C., Mohammad, R., Taub, J.W., Matherly, L.H., Transcriptional regulation of the human reduced folate carrier in childhood acute lymphoblastic leukemia cells. Clin. Cancer Res. 12:2 (2006), 608–616.
33. Zhao, Y., Huang, H., Wei, G., Novel agents and biomarkers for acute lymphoid leukemia. J. Hemtol. Oncol., 6(1), 2013, 1.
34. Mullighan, C.G., Su, X., Zhang, J., Radtke, I., Phillips, L.A., Miller, C.B., Ma, J., Liu, W., Cheng, C., Schulman, B.A., Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N. Engl. J. Med. 360:5 (2009), 470–480.
35. Javierre, B.M., Rodriguez-Ubreva, J., Al-Shahrour, F., Corominas, M., Graña, O., Agirre, X., Pisano, D.G., Valencia, A., Roman-Gomez, J., Calasanz, M.J., Long-range epigenetic silencing associates with deregulation of Ikaros targets in colorectal cancer cells. Mol. Cancer Res. 9:8 (2011), 1139–1151.
36. Zhang, Z., Xu, Z., Wang, X., Wang, H., Yao, Z., Mu, Y., Ma, Z., Liu, Z., Ectopic Ikaros expression positively correlates with lung cancer progression. Anat. Rec. 296:6 (2013), 907–913.
37. Otsuki, T., Jaffe, E.S., Ueki, A., Involvement of INK4 family cyclin-dependent-kinase inhibitor genes in hematological malignancies. Kawasaki Med. J. 22:3 (1996), 109–138.
38. Bodoor, K., Haddad, Y., Alkhateeb, A., Al-Abbadi, A., Dowairi, M., Magableh, A., Bsoul, N., Ghabkari, A., DNA hypermethylation of cell cycle (p15 and p16) and apoptotic (p14, p53, DAPK and TMS1) genes in peripheral blood of leukemia patients. Asian Pacif. J. Cancer Prev. 15:1 (2014), 75–84.
39. Iacobucci, I., Ferrari, A., Lonetti, A., Papayannidis, C., Paoloni, F., Trino, S., Storlazzi, C.T., Ottaviani, E., Cattina, F., Impera, L., CDKN2A/B alterations impair prognosis in adult BCR-ABL1–positive acute lymphoblastic leukemia patients. Clin. Cancer Res. 17:23 (2011), 7413–7423.
40. Herman, J.G., Jen, J., Merlo, A., Baylin, S.B., Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B. Cancer Res. 56:4 (1996), 722–727.
41. Mai, H., Liu, X., Chen, Y., Li, C., Cao, L., Chen, X., Chen, S., Liu, G., Wen, F., Hypermethylation of p15 gene associated with an inferior poor long-term outcome in childhood acute lymphoblastic leukemia. J. Cancer Res. Clin. Oncol. 142:2 (2016), 497–504.
42. Sharma, V., Jha, A., Kumar, A., Bhatnagar, A., Narayan, G., Kaur, J., Curcumin-Mediated reversal of p15 Gene promoter methylation: implication in anti-neoplastic action against acute lymphoid Leukaemia cell line. Folia Biol. 61:2 (2014), 81–89.
43. Wong, I.H., Ng, M.H., Huang, D.P., Lee, J.C., Aberrant p15 promoter methylation in adult and childhood acute leukemias of nearly all morphologic subtypes: potential prognostic implications. Blood 95:6 (2000), 1942–1949.
44. Takeuchi, S., Matsushita, M., Zimmermann, M., Ikezoe, T., Komatsu, N., Seriu, T., Schrappe, M., Bartram, C.R., Koeffler, H.P., Clinical significance of aberrant DNA methylation in childhood acute lymphoblastic leukemia. Leuk. Res. 35:10 (2011), 1345–1349.
45. Tsellou, E., Troungos, C., Moschovi, M., Athanasiadou-Piperopoulou, F., Polychronopoulou, S., Kosmidis, H., Kalmanti, M., Hatzakis, A., Dessypris, N., Kalofoutis, A., Hypermethylation of CpG islands in the promoter region of the p15INK4B gene in childhood acute leukaemia. Eur. J. Cancer 41:4 (2005), 584–589.
46. Chung, Y.R., Schatoff, E., Abdel-Wahab, O., Epigenetic alterations in hematopoietic malignancies. Int. J. Hematol. 96:4 (2012), 413–427.
47. Ito, S., D'Alessio, A.C., Taranova, O.V., Hong, K., Sowers, L.C., Zhang, Y., Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466:7310 (2010), 1129–1133.
48. Tahiliani, M., Koh, K.P., Shen, Y., Pastor, W.A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L.M., Liu, D.R., Aravind, L., Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:5929 (2009), 930–935.
49. Quivoron, C., Couronné, L., Della Valle, V., Lopez, C.K., Plo, I., Wagner-Ballon, O., Cruzeiro, M.Do, Delhommeau, F., Arnulf, B., Stern, M.-H., TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell 20:1 (2011), 25–38.
50. Lorsbach, R., Moore, J., Mathew, S., Raimondi, S., Mukatira, S., Downing, J., TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t (10; 11)(q22; q23). Leukemia, 17(3), 2003 (08876924).
51. Mascarenhas, J., Roper, N., Chaurasia, P., Hoffman, R., Epigenetic abnormalities in myeloproliferative neoplasms: a target for novel therapeutic strategies. Clin. Epigenetics, 2(2), 2011, 197.
52. Musialik, E., Bujko, M., Wypych, A., Matysiak, M., Siedlecki, J.A., TET2 promoter DNA methylation and expression analysis in pediatric B-cell acute lymphoblastic leukemia. Hematol. Rep., 6(1), 2014.
53. Chim, C., Wan, T., Fung, T., Wong, K., Methylation of TET2, CBL and CEBPA in Ph-negative myeloproliferative neoplasms. J. Clin. Pathol. 63:10 (2010), 942–946.
54. DiNardo, C., Gharibyan, V., Yang, H., Wei, Y., Pierce, S., Kantarjian, H., Garcia-Manero, G., Rytting, M., Impact of aberrant DNA methylation patterns including CYP1B1 methylation in adolescents and young adults with acute lymphocytic leukemia. Am. J. Hematol. 88:9 (2013), 784–789.
55. Tang, Y.M., Wo, Y.-Y.P., Stewart, J., Hawkins, A.L., Griffin, C.A., Sutter, T.R., Greenlee, W.F., Isolation and characterization of the human cytochrome P450 CYP1B1 gene. J. Biol. Chem. 271:45 (1996), 28324–28330.
56. Aydin-Sayitoglu, M., Hatirnaz, O., Erensoy, N., Ozbek, U., Role of CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 genes in the susceptibility to acute leukemias. Am. J. Hematol. 81:3 (2006), 162–170.
57. Van Driessche, A., Gao, L., Stauss, H., Ponsaerts, P., Van Bockstaele, D., Berneman, Z., Van Tendeloo, V., Antigen-specific cellular immunotherapy of leukemia. Leukemia 19:11 (2005), 1863–1871.
58. Das, D.N., Panda, P.K., Naik, P.P., Mukhopadhyay, S., Sinha, N., Bhutia, S.K., Phytotherapeutic approach: a new hope for polycyclic aromatic hydrocarbons induced cellular disorders, autophagic and apoptotic cell death. Toxicol. Mech. Meth., 2016, 1–54 just-accepted.
59. Kawai, M., Chen, J., Cheung, C.Y., Chang, T.K., Transcript profiling of cytochrome P450 genes in HL-60 human leukemic cells: upregulation of CYP1B1 by all-trans-retinoic acid. Mol. Cell. Biochem. 248:1–2 (2003), 57–65.
60. Kim, I.W., Han, N., Burckart, G.J., Oh, J.M., Epigenetic Changes in Gene Expression for Drug‐Metabolizing Enzymes and Transporters. Pharmacother.: J. Hum. Pharmacol. Drug Ther. 34:2 (2014), 140–150.
61. Xia, Y., Hong, Q., Chen, X., Ye, H., Fang, L., Zhou, A., Gao, Y., Jiang, D., Duan, S., APC2 and CYP1B1 methylation changes in the bone marrow of acute myeloid leukemia patients during chemotherapy. Exp. Ther. Med. 12:5 (2016), 3047–3052.
62. Heller, G., Topakian, T., Altenberger, C., Cerny-Reiterer, S., Herndlhofer, S., Ziegler, B., Datlinger, P., Byrgazov, K., Bock, C., Mannhalter, C., Next-generation sequencing identifies major DNA methylation changes during progression of Ph+ chronic myeloid leukemia. Leukemia, 2016.
63. Kohlhase, J., Heinrich, M., Schubert, L., Liebers, M., Kispert, A., Laccone, F., Turnpenny, P., Winter, R.M., Reardon, W., Okihiro syndrome is caused by SALL4 mutations. Hum. Mol. Genet. 11:23 (2002), 2979–2987.
64. Al-Baradie, R., Yamada, K., Hilaire, C.S., Chan, W.-M., Andrews, C., McIntosh, N., Nakano, M., Martonyi, E.J., Raymond, W.R., Okumura, S., Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am. J. Hum. Genet. 71:5 (2002), 1195–1199.
65. Ueno, S., Lu, J., He, J., Li, A., Zhang, X., Ritz, J., Silberstein, L.E., Chai, L., Aberrant expression of SALL4 in acute B cell lymphoblastic leukemia: mechanism, function, and implication for a potential novel therapeutic target. Exp. Hematol. 42:4 (2014), 307–316 e8.
66. Wu, Q., Chen, X., Zhang, J., Loh, Y.-H., Low, T.-Y., Zhang, W., Zhang, W., Sze, S.-K., Lim, B., Ng, H.-H., Sall4 interacts with Nanog and co-occupies Nanog genomic sites in embryonic stem cells. J. Biol. Chem. 281:34 (2006), 24090–24094.
67. Feng, M., Huang, B., Du, Z., Xu, X., Chen, Z., DLC-1 as a modulator of proliferation, apoptosis and migration in Burkitt's lymphoma cells. Mol. Biol. Rep. 38:3 (2011), 1915–1920.
68. Liao, Y.-C., Lo, S.H., Deleted in liver cancer-1 (DLC-1): a tumor suppressor not just for liver. Int. J. Biochem. Cell Biol. 40:5 (2008), 843–847.
69. Qin, Y., Chu, B., Gong, W., Wang, J., Tang, Z., Shen, J., Quan, Z., The inhibitory effects of deleted in liver cancer 1 gene on gallbladder cancer growth through induction of cell cycle arrest and apoptosis. J. Gastroenterol. Hepatol. 29:5 (2014), 964–972.
70. Zhou, X., Yang, X.-Y., Popescu, N.C., Preclinical evaluation of combined antineoplastic effect of DLC1 tumor suppressor protein and suberoylanilide hydroxamic acid on prostate cancer cells. Biochem. Biophys. Res. Commun. 420:2 (2012), 325–330.
71. Ullmannova-Benson, V., Guan, M., Zhou, X., Tripathi, V., Yang, X.-Y., Zimonjic, D.B., Popescu, N.C., DLC1 tumor suppressor gene inhibits migration and invasion of multiple myeloma cells through RhoA GTPase pathway. Leukemia 23:2 (2009), 383–390.
72. Fu, H.-y., Wu, D.-s., Zhou, H.-r., Shen, J.-z., CpG island methylator phenotype and its relationship with prognosis in adult acute leukemia patients. Hematology 19:6 (2014), 329–337.
73. Zhou, J.-D., Wang, Y.-X., Zhang, T.-J., Yang, D.-q., Yao, D.-M., Guo, H., Yang, L., Ma, J.-C., Wen, X.-M., Yang, J., Epigenetic inactivation of DLX4 is associated with disease progression in chronic myeloid leukemia. Biochem. Biophys. Res. Commun. 463:4 (2015), 1250–1256.
74. Trinh, B.Q., The role and mechanism of the homeobox gene DLX4 in transforming growth factor B resistance in cancer. 2011.
75. Dell‘Orto, M.C., Banelli, B., Giarin, E., Accordi, B., Trentin, L., Romani, M., Kronnie, G.T., Basso, G., Down-regulation of DLX3 expression in MLL-AF4 childhood lymphoblastic leukemias is mediated by promoter region hypermethylation. Oncol. Rep., 18(2), 2007, 417.
76. Homminga, I., Pieters, R., Meijerink, J., NKL homeobox genes in leukemia. Leukemia 26:4 (2012), 572–581.
77. Zhou, J.-d., Zhang, T.-j., Wang, Y.-x., Yang, D.-q., Yang, L., Ma, J.-c., Wen, X.-m., Yang, J., Lin, J., Qian, J., DLX4 hypermethylation is a prognostically adverse indicator in de novo acute myeloid leukemia. Tumor Biol. 37:7 (2016), 8951–8960.
78. Samuel, S., Naora, H., Homeobox gene expression in cancer: insights from developmental regulation and deregulation. Eur. J. Cancer 41:16 (2005), 2428–2437.
79. Tan, Y., Cheung, M., Pei, J., Menges, C.W., Godwin, A.K., Testa, J.R., Upregulation of DLX5 promotes ovarian cancer cell proliferation by enhancing IRS-2-AKT signaling. Cancer Res. 70:22 (2010), 9197–9206.
80. Haga, S., Fu, S., Karp, J., Ross, D., Williams, D., Hankins, W., Behm, F., Ruscetti, F., Chang, M., Smith, B., BP1, a new homeobox gene, is frequently expressed in acute leukemias. Leukemia, 14(11), 2000, 1867.
81. Sato, H., Oka, T., Shinnou, Y., Kondo, T., Washio, K., Takano, M., Takata, K., Morito, T., Huang, X., Tamura, M., Multi-step aberrant CpG Island hyper-methylation is associated with the progression of adult T–cell leukemia/lymphoma. Am. J. Pathol. 176:1 (2010), 402–415.
82. Jiang, D., Hong, Q., Shen, Y., Xu, Y., Zhu, H., Li, Y., Xu, C., Ouyang, G., Duan, S., The diagnostic value of DNA methylation in leukemia: a systematic review and meta-analysis. PloS One, 9(5), 2014, e96822.
83. Yeh, C.-H., Bai, X.T., Moles, R., Ratner, L., Waldmann, T.A., Watanabe, T., Nicot, C., Mutation of epigenetic regulators TET2 and MLL3 in patients with HTLV-I-induced acute adult T-cell leukemia. Mol. Cancer, 15(1), 2016, 15.
84. Pei, J.-H., Luo, S.-Q., Zhong, Y., Chen, J.-H., Xiao, H.-W., Hu, W.-X., The association between non-hodgkin lymphoma and methylation of p73. Tumor Biol., 32(6), 2011, 1133.
85. Chen, X., Zhang, H., Li, P., Yang, Z., Qin, L., Mo, W., Gene expression of WWOX, FHIT and p73 in acute lymphoblastic leukemia. Oncol. Lett. 6:4 (2013), 963–969.
86. Kaghad, M., Bonnet, H., Yang, A., Creancier, L., Biscan, J.-C., Valent, A., Minty, A., Chalon, P., Lelias, J.-M., Dumont, X., Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90:4 (1997), 809–819.
87. Jha, A.K., Nikbakht, M., Jain, V., Sehgal, A., Capalash, N., Kaur, J., Promoter hypermethylation of p73 and p53 genes in cervical cancer patients among north Indian population. Mol. Biol. Rep. 39:9 (2012), 9145–9157.
88. Alhosin, M., Abusnina, A., Achour, M., Sharif, T., Muller, C., Peluso, J., Chataigneau, T., Lugnier, C., Schini-Kerth, V.B., Bronner, C., Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1. Biochem. Pharmacol. 79:9 (2010), 1251–1260.
89. Levrero, M., De Laurenzi, V., Costanzo, A., Gong, J., Wang, J., Melino, G., The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J. Cell Sci. 113:10 (2000), 1661–1670.
90. Song, D., Yue, L., Wu, G., Ma, S., Yang, H., Liu, Q., Zhang, D., Xia, Z., Jia, J., Wang, J., Evaluation of promoter hypomethylation and expression of p73 as a diagnostic and prognostic biomarker in Wilms’ tumour. J. Clin. Pathol., 2015 jclinpath-2015-203150.
91. Alexandrova, E.M., Moll, U.M., Role of p53 family members p73 and p63 in human hematological malignancies. Leuk. Lymphoma 53:11 (2012), 2116–2129.
92. Singh, P.K., Mistry, K., Epigenetics of Acute lymphocytic leukemia. Quest, 2(2), 2014, 18.
93. Aqeilan, R.I., Pekarsky, Y., Herrero, J.J., Palamarchuk, A., Letofsky, J., Druck, T., Trapasso, F., Han, S.-Y., Melino, G., Huebner, K., Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Proc. Natl. Acad. Sci. U. S. A. 101:13 (2004), 4401–4406.
94. Pluta, A., Nyman, U., Joseph, B., Robak, T., Zhivotovsky, B., Smolewski, P., The role of p73 in hematological malignancies. Leukemia, 20(5), 2006, 757.
95. Hatzimichael, E., Dasoula, A., Benetatos, L., Makis, A., Stebbing, J., Crook, T., Syrrou, M., Bourantas, K.L., The absence of CDKN1C (p57KIP2) promoter methylation in myeloid malignancies also characterizes plasma cell neoplasms. Br. J. Haematol. 141:4 (2008), 557–558.
96. Shen, L., Toyota, M., Kondo, Y., Obata, T., Daniel, S., Pierce, S., Imai, K., Kantarjian, H.M., Issa, J.-P.J., Garcia-Manero, G., Aberrant DNA methylation of p57KIP2 identifies a cell-cycle regulatory pathway with prognostic impact in adult acute lymphocytic leukemia. Blood 101:10 (2003), 4131–4136.
97. Kikuchi, T., Toyota, M., Itoh, F., Suzuki, H., Obata, T., Yamamoto, H., Kakiuchi, H., Kusano, M., Issa, J.-P.J., Tokino, T., Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors. Oncogene, 21(17), 2002, 2741.
98. Kuang, S., Ling, X., Sanchez-Gonzalez, B., Yang, H., Andreeff, M., Garcia-Manero, G., Differential tumor suppressor properties and transforming growth factor-β responsiveness of p57KIP2 in leukemia cells with aberrant p57KIP2 promoter DNA methylation. Oncogene 26:10 (2007), 1439–1448.
99. Hagiwara, K., Li, Y., Kinoshita, T., Kunishma, S., Ohashi, H., Hotta, T., Nagai, H., Aberrant DNA methylation of the p57KIP2 gene is a sensitive biomarker for detecting minimal residual disease in diffuse large B cell lymphoma. Leuk. Res. 34:1 (2010), 50–54.
100. Saiki, J., McCredie, K., Vietti, T., Hewlett, J., Morrison, F., Costanzi, J., Stuckey, W., Whitecar, J., Hoogstraten, B., 5‐azacytidine in acute leukemia. Cancer 42:5 (1978), 2111–2114.
101. Saiki, J., Bodey, G., Hewlett, J., Amare, M., Morrision, F., Wilson, H., Linman, J., Effect of schedule on activity and toxicity of 5‐azacytidine in acute leukemia: a southwest oncology group study. Cancer 47:7 (1981), 1739–1742.
102. Braiteh, F., Soriano, A.O., Garcia-Manero, G., Hong, D., Johnson, M.M., Silva, L.D.P., Yang, H., Alexander, S., Wolff, J., Kurzrock, R., Phase I study of epigenetic modulation with 5-azacytidine and valproic acid in patients with advanced cancers. Clin. Cancer Res. 14:19 (2008), 6296–6301.
103. Goodyear, O.C., Dennis, M., Jilani, N.Y., Loke, J., Siddique, S., Ryan, G., Nunnick, J., Khanum, R., Raghavan, M., Cook, M., Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood 119:14 (2012), 3361–3369.
104. Itzykson, R., Kosmider, O., Cluzeau, T., Mansat-De Mas, V., Dreyfus, F., Beyne-Rauzy, O., Quesnel, B., Vey, N., Gelsi-Boyer, V., Raynaud, S., Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia 25:7 (2011), 1147–1152.
105. Bhalla, K.N., Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies. J. Clin. Oncol. 23:17 (2005), 3971–3993.
106. Paulson, K., Kumar, R., Ahsanuddin, A., Seftel, M.D., Azacytidine as a novel agent in the treatment of acute lymphoblastic leukemia. Leuk. Lymphoma 52:1 (2011), 134–136.
107. Lyko, F., Brown, R., DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J. Natl. Cancer Inst. 97:20 (2005), 1498–1506.
108. Issa, J.-P.J., Garcia-Manero, G., Giles, F.J., Mannari, R., Thomas, D., Faderl, S., Bayar, E., Lyons, J., Rosenfeld, C.S., Cortes, J., Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 103:5 (2004), 1635–1640.
109. Yang, A.S., Doshi, K.D., Choi, S.-W., Mason, J.B., Mannari, R.K., Gharybian, V., Luna, R., Rashid, A., Shen, L., Estecio, M.R., DNA methylation changes after 5-aza-2′-deoxycytidine therapy in patients with leukemia. Cancer Res. 66:10 (2006), 5495–5503.
110. Yanez, L., Bermudez, A., Richard, C., Bureo, E., Iriondo, A., Successful induction therapy with decitabine in refractory childhood acute lymphoblastic leukemia. Leukemia 23:7 (2009), 1342–1344.
111. Daskalakis, M., Nguyen, T.T., Nguyen, C., Guldberg, P., Köhler, G., Wijermans, P., Jones, P.A., Lübbert, M., Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2′-deoxycytidine (decitabine) treatment. Blood 100:8 (2002), 2957–2964.