Therapeutic inhibition of USP7-PTEN network in chronic lymphocytic leukemia: A strategy to overcome TP53 mutated/ deleted clones

Oncotarget

Volumn 8, Issue 22, 2017, Pages 35508-35522

  Carrà, Giovanna ^a   Panuzzo, Cristina ^a   Torti, Davide ^a,b   Parvis, Guido ^b,c   Crivellaro, Sabrina ^a   Familiari, Ubaldo ^b   Volante, Marco ^a,b   Morena, Deborah ^a   Lingua, Marcello Francesco ^a   Brancaccio, Mara ^a   Guerrasio, Angelo ^a   Pandolfi, Pier Paolo ^d   Saglio, Giuseppe ^a,b,c   Taulli, Riccardo ^a   Morotti, Alessandro ^a  

^a UNIVERSITY OF TURIN   (Italy)

^b SAN LUIGI GONZAGA HOSPITAL   (Italy)

^c Bone Marrow Transplant Unit   (Italy)

^d HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Chronic lymphocytic leukemia; MiR181; MiR338; PTEN; USP7

Indexed keywords

ANTINEOPLASTIC AGENT; CASEIN KINASE II; DEUBIQUITINASE; MICRORNA; MICRORNA 181B; MICRORNA 338 3P; P 5091; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN P53; UNCLASSIFIED DRUG; USP7 PROTEIN; PTEN PROTEIN, HUMAN; UBIQUITIN CARBOXYL TERMINAL HYDROLASE 7; USP7 PROTEIN, HUMAN;

APOPTOSIS; ARTICLE; CELL GROWTH; CELL VIABILITY; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; DOSE RESPONSE; DRUG MECHANISM; DRUG POTENCY; ENZYME INHIBITION; GENE; GROWTH INHIBITION; HUMAN; HUMAN CELL; IC50; MOLECULARLY TARGETED THERAPY; POSTTRANSCRIPTION REGULATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROCESSING; TP53 GENE; TRANSCRIPTION REGULATION; UBIQUITINATION; UPREGULATION; USP7 GENE; BIOLOGICAL MODEL; CELL PROLIFERATION; DRUG EFFECT; GENE DELETION; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORK; GENETICS; METABOLISM; MUTATION; PROTEIN TRANSPORT; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL LINE, TUMOR; CELL PROLIFERATION; GENE DELETION; GENE EXPRESSION REGULATION, LEUKEMIC; GENE REGULATORY NETWORKS; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MODELS, BIOLOGICAL; MUTATION; PROTEIN TRANSPORT; PTEN PHOSPHOHYDROLASE; TUMOR SUPPRESSOR PROTEIN P53; UBIQUITIN-SPECIFIC PEPTIDASE 7; UP-REGULATION;

EID: 85021711548     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.16348     Document Type: Article

References (63)

1. Nabhan C, Rosen ST. Chronic lymphocytic leukemia: a clinical review. JAMA. 2014; 312: 2265-76. doi: 10.1001/ jama.2014.14553
2. Gruber M, Wu CJ. Evolving understanding of the CLL genome. Semin Hematol. 2014; 51: 177-87. doi: 10.1053/j. seminhematol.2014.05.004
3. Delgado J, Baumann T, Santacruz R, Montserrat E. New treatment options for chronic lymphocytic leukemia. Expert Opin Pharmacother. 2014; 15: 823-32. doi: 10.1517/14656566.2014.891017
4. Rossi D, Ciardullo C, Spina V, Gaidano G. Molecular bases of chronic lymphocytic leukemia in light of new treatments. Immunol Lett. 2013; 155: 51-5. doi: 10.1016/j. imlet.2013.09.010
5. Gaidano G, Foà R, Dalla-Favera R. Molecular pathogenesis of chronic lymphocytic leukemia. J Clin Invest. 2012; 122: 3432-8. doi: 10.1172/JCI64101
6. Zenz T, Mertens D, Küppers R, Döhner H, Stilgenbauer S. From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer. 2010; 10: 37-50. doi: 10.1038/ nrc2764
7. Baliakas P, Hadzidimitriou A, Sutton LA, Rossi D, Minga E, Villamor N, Larrayoz M, Kminkova J, Agathangelidis A, Davis Z, Tausch E, Stalika E, Kantorova B, et al. Recurrent mutations refine prognosis in chronic lymphocytic leukemia. Leukemia. 2015; 29: 329-36. doi: 10.1038/ leu.2014.196
8. Zent CS, Burack WR. Mutations in chronic lymphocytic leukemia and how they affect therapy choice: focus on NOTCH1, SF3B1, and TP53. Hematol Educ Program Am Soc Hematol Am Soc Hematol Educ Program. 2014; 2014: 119-24. doi: 10.1182/asheducation-2014.1.119
9. Wilson WH. Progress in Chronic Lymphocytic Leukemia with Targeted Therapy. N Engl J Med. 2016; 374: 386-8. doi: 10.1056/NEJMe1515235
10. Chang JE, Kahl BS. PI3-kinase inhibitors in chronic lymphocytic leukemia. Curr Hematol Malig Rep. 2014; 9: 33-43. doi: 10.1007/s11899-013-0189-7
11. Xia B, Qu F, Yuan T, Zhang Y. Targeting Bruton's tyrosine kinase signaling as an emerging therapeutic agent of B-cell malignancies. Oncol Lett. 2015; 10: 3339-44. doi: 10.3892/ ol.2015.3802
12. Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR, Hillmen P, Stephens DM, Ghia P, et al. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016; 374: 323-32. doi: 10.1056/NEJMoa1509981
13. Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DCS, Hymowitz SG, Jin S, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013; 19: 202-8. doi: 10.1038/nm.3048
14. Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, Kipps TJ, Anderson MA, Brown JR, Gressick L, Wong S, Dunbar M, Zhu M, et al. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016; 374: 311-22. doi: 10.1056/ NEJMoa1513257
15. Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn I, Ghia P, Eradat H, Ervin T, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014; 370: 997-1007. doi: 10.1056/NEJMoa1315226
16. Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Devereux S, Barr PM, Furman RR, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014; 371: 213-23. doi: 10.1056/ NEJMoa1400376
17. Chauhan D, Tian Z, Nicholson B, Kumar KGS, Zhou B, Carrasco R, McDermott JL, Leach CA, Fulcinniti M, Kodrasov MP, Weinstock J, Kingsbury WD, Hideshima T, et al. A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Cancer Cell. 2012; 22: 345-58. doi: 10.1016/j.ccr.2012.08.007
18. Cummins JM, Vogelstein B. HAUSP is required for p53 destabilization. Cell Cycle Georget Tex. 2004; 3: 689-92
19. Song MS, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J, Pandolfi PP. The deubiquitinylation and localization of PTEN are regulated by a HAUSPPML network. Nature. 2008; 455: 813-7. doi: 10.1038/ nature07290
20. Morotti A, Panuzzo C, Crivellaro S, Pergolizzi B, Familiari U, Berger AH, Saglio G, Pandolfi PP. BCRABL disrupts PTEN nuclear-cytoplasmic shuttling through phosphorylation-dependent activation of HAUSP. Leukemia. 2014; 28: 1326-33. doi: 10.1038/leu.2013.370
21. van der Horst A, de Vries-Smits AMM, Brenkman AB, van Triest MH, van den Broek N, Colland F, Maurice MM, Burgering BMT. FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol. 2006; 8: 1064-73. doi: 10.1038/ncb1469
22. Wickremasinghe RG, Prentice AG, Steele AJ. p53 and Notch signaling in chronic lymphocytic leukemia: clues to identifying novel therapeutic strategies. Leukemia. 2011; 25: 1400-7. doi: 10.1038/leu.2011.103
23. Leupin N, Cenni B, Novak U, Hügli B, Graber HU, Tobler A, Fey MF. Disparate expression of the PTEN gene: a novel finding in B-cell chronic lymphocytic leukaemia (B-CLL). Br J Haematol. 2003; 121: 97-100
24. Zou ZJ, Zhang R, Fan L, Wang L, Fang C, Zhang LN, Yang S, Li YY, Li JY, Xu W. Low expression level of phosphatase and tensin homolog deleted on chromosome ten predicts poor prognosis in chronic lymphocytic leukemia. Leuk Lymphoma. 2013; 54: 1159-64. doi:10.3109/10428194.2012.733880
25. Zou Z-J, Fan L, Wang L, Xu J, Zhang R, Tian T, Li J-Y, Xu W. miR-26a and miR-214 down-regulate expression of the PTEN gene in chronic lymphocytic leukemia, but not PTEN mutation or promoter methylation. Oncotarget. 2015; 6: 1276-85. doi: 10.18632/oncotarget.2626
26. Shehata M, Schnabl S, Demirtas D, Hilgarth M, Hubmann R, Ponath E, Badrnya S, Lehner C, Hoelbl A, Duechler M, Gaiger A, Zielinski C, Schwarzmeier JD, et al. Reconstitution of PTEN activity by CK2 inhibitors and interference with the PI3-K/Akt cascade counteract the antiapoptotic effect of human stromal cells in chronic lymphocytic leukemia. Blood. 2010; 116: 2513-21. doi:10.1182/blood-2009-10-248054
27. Martins LR, Lúcio P, Silva MC, Anderes KL, Gameiro P, Silva MG, Barata JT. Targeting CK2 overexpression and hyperactivation as a novel therapeutic tool in chronic lymphocytic leukemia. Blood. 2010; 116: 2724-31. doi:10.1182/blood-2010-04-277947
28. Best OG, Mulligan SP. The phosphoinositide 3-kinase pathway in chronic lymphocytic leukemia: evidence for phosphatase and tensin homolog deletion on chromosome 10 deregulation. Leuk Lymphoma. 2013; 54: 1123-4. doi:10.3109/10428194.2012.746685
29. Martins LR, Lúcio P, Silva MC, Gameiro P, Silva MG, Barata JT. On CK2 regulation of chronic lymphocytic leukemia cell viability. Mol Cell Biochem. 2011; 356: 51-
30. doi: 10.1007/s11010-011-0947-6
31. Martins LR, Perera Y, Lúcio P, Silva MG, Perea SE, Barata JT. Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor. Oncotarget. 2014; 5: 258-63. doi: 10.18632/ oncotarget.1513
32. Marchenko ND, Hanel W, Li D, Becker K, Reich N, Moll UM. Stress-mediated nuclear stabilization of p53 is regulated by ubiquitination and importin-alpha3 binding. Cell Death Differ. 2010; 17: 255-67. doi: 10.1038/ cdd.2009.173
33. Becker K, Marchenko ND, Maurice M, Moll UM. Hyperubiquitylation of wild-type p53 contributes to cytoplasmic sequestration in neuroblastoma. Cell Death Differ. 2007; 14: 1350-60. doi: 10.1038/sj.cdd.4402126
34. Khoronenkova SV, Dianova II, Ternette N, Kessler BM, Parsons JL, Dianov GL. ATM-dependent downregulation of USP7/HAUSP by PPM1G activates p53 response to DNA damage. Mol Cell. 2012; 45: 801-13. doi: 10.1016/j. molcel.2012.01.021
35. Morotti A, Panuzzo C, Crivellaro S, Carrà G, Guerrasio A, Saglio G. HAUSP compartmentalization in chronic myeloid leukemia. Eur J Haematol. 2015; 94: 318-21. doi: 10.1111/ ejh.12422
36. Maura F, Cutrona G, Mosca L, Matis S, Lionetti M, Fabris S, Agnelli L, Colombo M, Massucco C, Ferracin M, Zagatti B, Reverberi D, Gentile M, et al. Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia. Leuk Lymphoma. 2015; 56: 3150-8. doi:10.3109/10428194.2015.1028051
37. Giza DE, Calin GA. microRNA and Chronic Lymphocytic Leukemia. Adv Exp Med Biol. 2015; 889: 23-40. doi:10.1007/978-3-319-23730-5_2
38. Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V, Volinia S, Alder H, Liu CG, Rassenti L, Calin GA, Hagan JP, Kipps T, et al. Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res. 2006; 66: 11590-3. doi:10.1158/0008-5472.CAN-06-3613
39. Balatti V, Pekarky Y, Rizzotto L, Croce CM. miR deregulation in CLL. Adv Exp Med Biol. 2013; 792: 309-
40. doi: 10.1007/978-1-4614-8051-8_14
41. Silva A, Yunes JA, Cardoso BA, Martins LR, Jotta PY, Abecasis M, Nowill AE, Leslie NR, Cardoso AA, Barata JT. PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability. J Clin Invest. 2008; 118: 3762-74. doi: 10.1172/ JCI34616
42. Prins RC, Burke RT, Tyner JW, Druker BJ, Loriaux MM, Spurgeon SE. CX-4945, a selective inhibitor of casein kinase-2 (CK2), exhibits anti-tumor activity in hematologic malignancies including enhanced activity in chronic lymphocytic leukemia when combined with fludarabine and inhibitors of the B-cell receptor pathway. Leukemia. 2013; 27: 2094-6. doi: 10.1038/leu.2013.228
43. Piazza F, Manni S, Ruzzene M, Pinna LA, Gurrieri C, Semenzato G. Protein kinase CK2 in hematologic malignancies: reliance on a pivotal cell survival regulator by oncogenic signaling pathways. Leukemia. 2012; 26: 1174-9. doi: 10.1038/leu.2011.385
44. Martins LR, Lúcio P, Melão A, Antunes I, Cardoso BA, Stansfield R, Bertilaccio MTS, Ghia P, Drygin D, Silva MG, Barata JT. Activity of the clinical-stage CK2-specific inhibitor CX-4945 against chronic lymphocytic leukemia. Leukemia. 2014; 28: 179-82. doi: 10.1038/leu.2013.232
45. Martins LR, Perera Y, Lúcio P, Silva MG, Perea SE, Barata JT. Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor. Oncotarget. 2014; 5: 258-63. doi: 10.18632/ oncotarget.1513
46. Lee G, Oh TI, Um KB, Yoon H, Son J, Kim BM, Kim H-, Kim H, Kim YJ, Lee CS, Lim JH. Small-molecule inhibitors of USP7 induce apoptosis through oxidative and endoplasmic reticulum stress in cancer cells. Biochem Biophys Res Commun. 2016; 470: 181-6. doi: 10.1016/j. bbrc.2016.01.021
47. Fan YH, Cheng J, Vasudevan SA, Dou J, Zhang H, Patel RH, Ma IT, Rojas Y, Zhao Y, Yu Y, Zhang H, Shohet JM, Nuchtern JG, et al. USP7 inhibitor P22077 inhibits neuroblastoma growth via inducing p53-mediated apoptosis. Cell Death Dis. 2013; 4: e867. doi: 10.1038/cddis.2013.400
48. Reverdy C, Conrath S, Lopez R, Planquette C, Atmanene C, Collura V, Harpon J, Battaglia V, Vivat V, Sippl W, Colland F. Discovery of specific inhibitors of human USP7/ HAUSP deubiquitinating enzyme. Chem Biol. 2012; 19: 467-77. doi: 10.1016/j.chembiol.2012.02.007
49. Menard R, Sulea T. Selective inhibition of USP7. Chem Biol. 2012; 19: 437-8. doi: 10.1016/j.chembiol.2012.04.001
50. Colland F. The therapeutic potential of deubiquitinating enzyme inhibitors. Biochem Soc Trans. 2010; 38: 137-43. doi: 10.1042/BST0380137
51. Colland F, Formstecher E, Jacq X, Reverdy C, Planquette C, Conrath S, Trouplin V, Bianchi J, Aushev VN, Camonis J, Calabrese A, Borg-Capra C, Sippl W, et al. Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Mol Cancer Ther. 2009; 8: 2286-95. doi: 10.1158/1535-7163.MCT-09-0097
52. Popovic D, Vucic D, Dikic I. Ubiquitination in disease pathogenesis and treatment. Nat Med. 2014; 20: 1242-53. doi: 10.1038/nm.3739
53. Fruman DA, Cantley LC. Idelalisib-a PI3Kd inhibitor for B-cell cancers. N Engl J Med. 2014; 370: 1061-2. doi:10.1056/NEJMe1400055
54. van der Horst A, de Vries-Smits AMM, Brenkman AB, van Triest MH, van den Broek N, Colland F, Maurice MM, Burgering BMT. FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol. 2006; 8: 1064-73. doi: 10.1038/ncb1469
55. Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012; 13: 283-96. doi: 10.1038/nrm3330
56. Song MS, Carracedo A, Salmena L, Song SJ, Egia A, Malumbres M, Pandolfi PP. Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphataseindependent manner. Cell. 2011; 144: 187-99. doi:10.1016/j.cell.2010.12.020
57. Shen WH, Balajee AS, Wang J, Wu H, Eng C, Pandolfi PP, Yin Y. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell. 2007; 128: 157-70. doi:10.1016/j.cell.2006.11.042
58. Bassi C, Ho J, Srikumar T, Dowling RJO, Gorrini C, Miller SJ, Mak TW, Neel BG, Raught B, Stambolic V. Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress. Science. 2013; 341: 395-9. doi: 10.1126/ science.1236188
59. Rossi D, Khiabanian H, Spina V, Ciardullo C, Bruscaggin A, Famà R, Rasi S, Monti S, Deambrogi C, De Paoli L, Wang J, Gattei V, Guarini A, et al. Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia. Blood. 2014; 123: 2139-47. doi: 10.1182/ blood-2013-11-539726
60. Bosco R, Rabusin M, Voltan R, Celeghini C, Corallini F, Capitani S, Secchiero P. Anti-leukemic activity of dasatinib in both p53(wild-type) and p53(mutated) B malignant cells. Invest New Drugs. 2012; 30: 417-22. doi: 10.1007/s10637-010-9564-6
61. Trotman LC, Wang X, Alimonti A, Chen Z, Teruya-Feldstein J, Yang H, Pavletich NP, Carver BS, Cordon-Cardo C, Erdjument-Bromage H, Tempst P, Chi S-G, Kim H-J, et al. Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell. 2007; 128: 141-56. doi:10.1016/j.cell.2006.11.040
62. Di Savino A, Panuzzo C, Rocca S, Familiari U, Piazza R, Crivellaro S, Carrà G, Ferretti R, Fusella F, Giugliano E, Camporeale A, Franco I, Miniscalco B, et al. Morgana acts as an oncosuppressor in chronic myeloid leukemia. Blood. 2015; 125: 2245-53. doi: 10.1182/blood-2014-05-575001
63. Taulli R, Bersani F, Foglizzo V, Linari A, Vigna E, Ladanyi M, Tuschl T, Ponzetto C. The muscle-specific microRNA miR-206 blocks human rhabdomyosarcoma growth in xenotransplanted mice by promoting myogenic differentiation. J Clin Invest. 2009; 119: 2366-78. doi:10.1172/JCI38075