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Expert Review of Anticancer Therapy Volume 11, 2011 - Issue 9
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Theme: Leukemia/Lymphoma - Review

Therapeutic potential of Notch inhibition in T-cell acute lymphoblastic leukemia: rationale, caveats and promises

Leonor M Sarmento Cancer Biology Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisbon, Portugal; Cancer Biology Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisbon, Portugal
&
João T Barata Cancer Biology Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisbon, Portugal;[email protected]
Pages 1403-1415 | Published online: 10 Jan 2014

References

  • Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet371(9617), 1030–1043 (2008).
  • Aifantis I, Raetz E, Buonamici S. Molecular pathogenesis of T-cell leukaemia and lymphoma. Nat. Rev. Immunol.8(5), 380–390 (2008).
  • Grabher C, Von Boehmer H, Look AT. Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat. Rev. Cancer6(5), 347–359 (2006).
  • Ellisen LW, Bird J, West DC et al. TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell66(4), 649–661 (1991).
  • Weng AP, Ferrando AA, Lee W et al. Activating mutations of Notch-1 in human T cell acute lymphoblastic leukemia. Science306(5694), 269–271 (2004).
  • Aster JC, Pear WS, Blacklow SC. Notch signaling in leukemia. Annu. Rev. Pathol.3, 587–613 (2008).
  • Palomero T, Ferrando A. Therapeutic targeting of NOTCH1 signaling in T-cell acute lymphoblastic leukemia. Clin. Lymphoma Myeloma9(Suppl. 3), S205–S210 (2009).
  • Kopan R, Goate A. A common enzyme connects Notch signaling and Alzheimer’s disease. Genes Dev.14(22), 2799–2806 (2000).
  • Schweisguth F. Regulation of Notch signaling activity. Curr. Biol.14(3), R129–R138 (2004).
  • Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell137(2), 216–233 (2009).
  • Kovall RA, Blacklow SC. Mechanistic insights into Notch receptor signaling from structural and biochemical studies. Curr. Top. Dev. Biol.92, 31–71 (2010).
  • Sultana DA, Bell JJ, Zlotoff DA, De Obaldia ME, Bhandoola A. Eliciting the T cell fate with Notch. Semin. Immunol.22(5), 254–260 (2010).
  • Pui JC, Allman D, Xu L et al. Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity11(3), 299–308 (1999).
  • Radtke F, Wilson A, Stark G et al. Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity10(5), 547–558 (1999).
  • Maillard I, Weng AP, Carpenter AC et al. Mastermind critically regulates Notch-mediated lymphoid cell fate decisions. Blood104(6), 1696–1702 (2004).
  • Jaleco AC, Neves H, Hooijberg E et al. Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation. J. Exp. Med.194(7), 991–1002 (2001).
  • Hozumi K, Mailhos C, Negishi N et al. Delta-like 4 is indispensable in thymic environment specific for T cell development. J. Exp. Med.205(11), 2507–2513 (2008).
  • Koch U, Fiorini E, Benedito R et al. Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment. J. Exp. Med.205(11), 2515–2523 (2008).
  • Yashiro-Ohtani Y, Ohtani T, Pear WS. Notch regulation of early thymocyte development. Semin. Immunol.22(5), 261–269 (2010).
  • Ciofani M, Zuniga-Pflucker JC. The thymus as an inductive site for T lymphopoiesis. Annu. Rev. Cell Dev. Biol.23, 463–493 (2007).
  • Weng AP, Millholland JM, Yashiro-Ohtani Y et al. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev.20(15), 2096–2109 (2006).
  • Palomero T, Lim WK, Odom DT et al. NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc. Natl Acad. Sci. USA103(48), 18261–18266 (2006).
  • Sharma VM, Calvo JA, Draheim KM et al. Notch1 contributes to mouse T-cell leukemia by directly inducing the expression of c-myc. Mol. Cell Biol.26(21), 8022–8031 (2006).
  • Erikson J, Finger L, Sun L et al. Deregulation of c-myc by translocation of the alpha-locus of the T-cell receptor in T-cell leukemias. Science232(4752), 884–886 (1986).
  • Joshi I, Minter LM, Telfer J et al. Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. Blood113(8), 1689–1698 (2009).
  • Sarmento LM, Huang H, Limon A et al. Notch1 modulates timing of G1-S progression by inducing SKP2 transcription and p27 Kip1 degradation. J. Exp. Med.202(1), 157–168 (2005).
  • Dohda T, Maljukova A, Liu L et al. Notch signaling induces SKP2 expression and promotes reduction of p27Kip1 in T-cell acute lymphoblastic leukemia cell lines. Exp. Cell Res.313(14), 3141–3152 (2007).
  • Barata JT, Cardoso AA, Nadler LM, Boussiotis VA. Interleukin-7 promotes survival and cell cycle progression of T-cell acute lymphoblastic leukemia cells by down-regulating the cyclin-dependent kinase inhibitor p27(kip1). Blood98(5), 1524–1531 (2001).
  • Gonzalez-Garcia S, Garcia-Peydro M, Martin-Gayo E et al. CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7Rα gene expression in early human thymopoiesis and leukemia. J. Exp. Med.206(4), 779–791 (2009).
  • Barata JT, Silva A, Brandao JG, Nadler LM, Cardoso AA, Boussiotis VA. Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells. J. Exp. Med.200(5), 659–669 (2004).
  • Barata JT, Cardoso AA, Boussiotis VA. Interleukin-7 in T-cell acute lymphoblastic leukemia: an extrinsic factor supporting leukemogenesis? Leuk. Lymphoma46(4), 483–495 (2005).
  • Barata JT, Keenan TD, Silva A, Nadler LM, Boussiotis VA, Cardoso AA. Common γ chain-signaling cytokines promote proliferation of T-cell acute lymphoblastic leukemia. Haematologica89(12), 1459–1467 (2004).
  • Weng AP, Nam Y, Wolfe MS et al. Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of Notch signaling. Mol. Cell Biol.23(2), 655–664 (2003).
  • Kawamata S, Du C, Li K, Lavau C. Overexpression of the Notch target genes HES in vivo induces lymphoid and myeloid alterations. Oncogene21(24), 3855–3863 (2002).
  • Wendorff AA, Koch U, Wunderlich FT et al. HES1 is a critical but context-dependent mediator of canonical Notch signaling in lymphocyte development and transformation. Immunity33(5), 671–684 (2010).
  • Palomero T, Sulis ML, Cortina M et al. Mutational loss of PTEN induces resistance to Notch1 inhibition in T-cell leukemia. Nat. Med.13(10), 1203–1210 (2007).
  • Murata K, Hattori M, Hirai N et al. HES1 directly controls cell proliferation through the transcriptional repression of p27KIP1. Mol. Cell Biol.25(10), 4262–4271 (2005).
  • Espinosa L, Cathelin S, D’altri T et al. The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia. Cancer Cell18(3), 268–281 (2010).
  • Pear WS, Aster JC, Scott ML et al. Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. J. Exp. Med.183(5), 2283–2291 (1996).
  • Girard L, Hanna Z, Beaulieu N et al. Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis. Genes Dev.10(15), 1930–1944 (1996).
  • Ferrando AA, Look AT. Clinical implications of recurring chromosomal and associated molecular abnormalities in acute lymphoblastic leukemia. Semin. Hematol.37(4), 381–395 (2000).
  • Sulis ML, Williams O, Palomero T et al. Notch1 extracellular juxtamembrane expansion mutations in T-ALL. Blood112(3), 733–740 (2008).
  • Gordon WR, Roy M, Vardar-Ulu D et al. Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL. Blood113(18), 4381–4390 (2009).
  • Malecki MJ, Sanchez-Irizarry C, Mitchell JL et al. Leukemia-associated mutations within the Notch1 heterodimerization domain fall into at least two distinct mechanistic classes. Mol. Cell Biol.26(12), 4642–4651 (2006).
  • Aste-Amezaga M, Zhang N, Lineberger JE et al. Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors. PLoS One5(2), e9094 (2010).
  • Wu Y, Cain-Hom C, Choy L et al. Therapeutic antibody targeting of individual Notch receptors. Nature464(7291), 1052–1057 (2010).
  • O’Neil J, Grim J, Strack P et al. FBW7 mutations in leukemic cells mediate Notch pathway activation and resistance to γ-secretase inhibitors. J. Exp. Med.204(8), 1813–1824 (2007).
  • Thompson BJ, Buonamici S, Sulis ML et al. The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J. Exp. Med.204(8), 1825–1835 (2007).
  • Malyukova A, Dohda T, Von Der Lehr N et al. The tumor suppressor gene hCDC4 is frequently mutated in human T-cell acute lymphoblastic leukemia with functional consequences for Notch signaling. Cancer Res.67(12), 5611–5616 (2007).
  • Chiang MY, Xu L, Shestova O et al. Leukemia-associated NOTCH1 alleles are weak tumor initiators but accelerate K-ras-initiated leukemia. J. Clin. Invest.118(9), 3181–3194 (2008).
  • O’Neil J, Calvo J, Mckenna K et al. Activating Notch1 mutations in mouse models of T-ALL. Blood107(2), 781–785 (2006).
  • Dumortier A, Jeannet R, Kirstetter P et al. Notch activation is an early and critical event during T-cell leukemogenesis in Ikaros-deficient mice. Mol. Cell Biol.26(1), 209–220 (2006).
  • Lin YW, Nichols RA, Letterio JJ, Aplan PD. Notch1 mutations are important for leukemic transformation in murine models of precursor-T leukemia/lymphoma. Blood107(6), 2540–2543 (2006).
  • Maser RS, Choudhury B, Campbell PJ et al. Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature447(7147), 966–971 (2007).
  • Tsuji H, Ishii-Ohba H, Ukai H, Katsube T, Ogiu T. Radiation-induced deletions in the 5´ end region of Notch1 lead to the formation of truncated proteins and are involved in the development of mouse thymic lymphomas. Carcinogenesis24(7), 1257–1268 (2003).
  • Ashworth TD, Pear WS, Chiang MY et al. Deletion-based mechanisms of Notch1 activation in T-ALL: key roles for RAG recombinase and a conserved internal translational start site in Notch1. Blood116(25), 5455–5464 (2010).
  • Jeannet R, Mastio J, Macias-Garcia A et al. Oncogenic activation of the Notch1 gene by deletion of its promoter in Ikaros-deficient T-ALL. Blood116(25), 5443–5454 (2010).
  • Gomez-Del Arco P, Kashiwagi M, Jackson AF et al. Alternative promoter usage at the Notch1 locus supports ligand-independent signaling in T cell development and leukemogenesis. Immunity33(5), 685–698 (2010).
  • Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N. Engl. J. Med.350(15), 1535–1548 (2004).
  • Breit S, Stanulla M, Flohr T et al. Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. Blood108(4), 1151–1157 (2006).
  • Park MJ, Taki T, Oda M et al. FBXW7 and Notch1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma. Br. J. Haematol.145(2), 198–206 (2009).
  • Larson Gedman A, Chen Q, Kugel Desmoulin S et al. The impact of NOTCH1, FBW7 and PTEN mutations on prognosis and downstream signaling in pediatric T-cell acute lymphoblastic leukemia: a report from the Children’s Oncology Group. Leukemia23(8), 1417–1425 (2009).
  • Van Grotel M, Meijerink JP, Beverloo HB et al. The outcome of molecular-cytogenetic subgroups in pediatric T-cell acute lymphoblastic leukemia: a retrospective study of patients treated according to DCOG or COALL protocols. Haematologica91(9), 1212–1221 (2006).
  • Zhu YM, Zhao WL, Fu JF et al. NOTCH1 mutations in T-cell acute lymphoblastic leukemia: prognostic significance and implication in multifactorial leukemogenesis. Clin. Cancer Res.12(10), 3043–3049 (2006).
  • Asnafi V, Buzyn A, Le Noir S et al. NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study. Blood113(17), 3918–3924 (2009).
  • Mansour MR, Sulis ML, Duke V et al. Prognostic implications of Notch1 and Fbxw7 mutations in adults with T-cell acute lymphoblastic leukemia treated on the MRC UKALLXII/ECOG E2993 protocol. J. Clin. Oncol.27(26), 4352–4356 (2009).
  • Ferrando AA. The role of Notch1 signaling in T-ALL. Hematology Am. Soc. Hematol. Educ. Program.353–361 (2009).
  • Kox C, Zimmermann M, Stanulla M et al. The favorable effect of activating Notch1 receptor mutations on long-term outcome in T-ALL patients treated on the ALL-BFM 2000 protocol can be separated from FBXW7 loss of function. Leukemia24(12), 2005–2013 (2010).
  • Clappier E, Collette S, Grardel N et al. Notch1 and Fbxw7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T-cell acute lymphoblastic leukemia (T-ALL) treated on EORTC trials 58881 and 58951. Leukemia24(12), 2023–2031 (2010).
  • Buonamici S, Trimarchi T, Ruocco MG et al. CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia. Nature459(7249), 1000–1004 (2009).
  • De Strooper B, Annaert W, Cupers P et al. A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature398(6727), 518–522 (1999).
  • Hadland BK, Manley NR, Su D et al. γ-secretase inhibitors repress thymocyte development. Proc. Natl Acad. Sci. USA98(13), 7487–7491 (2001).
  • Deangelo DJ, Stone RM, Silverman LB et al. A Phase I clinical trial of the Notch inhibitor MK-0752 in patients with T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and other leukemias. J. Clin. Oncol.24(18S), 6585 (2006).
  • Van Es JH, Van Gijn ME, Riccio O et al. Notch/γ-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature435(7044), 959–963 (2005).
  • Wong GT, Manfra D, Poulet FM et al. Chronic treatment with the γ-secretase inhibitor LY-411,575 inhibits β-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J. Biol. Chem.279(13), 12876–12882 (2004).
  • Medyouf H, Gao X, Armstrong F et al. Acute T-cell leukemias remain dependent on Notch signaling despite PTEN and INK4A/ARF loss. Blood115(6), 1175–1184 (2010).
  • Welcker M, Clurman BE. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat. Rev. Cancer8(2), 83–93 (2008).
  • Foltz DR, Santiago MC, Berechid BE, Nye JS. Glycogen synthase kinase-3β modulates Notch signaling and stability. Curr. Biol.12(12), 1006–1011 (2002).
  • Wolfe MS. Secretase as a target for Alzheimer’s disease. Curr. Top. Med. Chem.2(4), 371–383 (2002).
  • Radtke F, Raj K. The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nat. Rev. Cancer3(10), 756–767 (2003).
  • Riccio O, Van Gijn ME, Bezdek AC et al. Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2. EMBO Rep.9(4), 377–383 (2008).
  • Masuda S, Kumano K, Suzuki T et al. Dual antitumor mechanisms of Notch signaling inhibitor in a T-cell acute lymphoblastic leukemia xenograft model. Cancer Sci.100(12), 2444–2450 (2009).
  • Noren-Nystrom U, Heyman M, Frisk P et al. Vascular density in childhood acute lymphoblastic leukaemia correlates to biological factors and outcome. Br. J. Haematol.146(5), 521–530 (2009).
  • Lewis HD, Leveridge M, Strack PR et al. Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of Notch signaling. Chem. Biol.14(2), 209–219 (2007).
  • Tammam J, Ware C, Efferson C et al. Down-regulation of the Notch pathway mediated by a γ-secretase inhibitor induces anti-tumour effects in mouse models of T-cell leukaemia. Br. J. Pharmacol.158(5), 1183–1195 (2009).
  • Moellering RE, Cornejo M, Davis TN et al. Direct inhibition of the NOTCH transcription factor complex. Nature462(7270), 182–188 (2009).
  • Yan XQ, Sarmiento U, Sun Y et al. A novel Notch ligand, Dll4, induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer. Blood98(13), 3793–3799 (2001).
  • Allman D, Karnell FG, Punt JA et al. Separation of Notch1 promoted lineage commitment and expansion/transformation in developing T cells. J. Exp. Med.194(1), 99–106 (2001).
  • Campese AF, Garbe AI, Zhang F, Grassi F, Screpanti I, Von Boehmer H. Notch1-dependent lymphomagenesis is assisted by but does not essentially require pre-TCR signaling. Blood108(1), 305–310 (2006).
  • Margolin AA, Palomero T, Sumazin P, Califano A, Ferrando AA, Stolovitzky G. ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes. Proc. Natl Acad. Sci. USA106(1), 244–249 (2009).
  • Chan SM, Weng AP, Tibshirani R, Aster JC, Utz PJ. Notch signals positively regulate activity of the mTOR pathway in T-cell acute lymphoblastic leukemia. Blood110(1), 278–286 (2007).
  • Vilimas T, Mascarenhas J, Palomero T et al. Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia. Nat. Med.13(1), 70–77 (2007).
  • Datta SR, Dudek H, Tao X et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell91(2), 231–241 (1997).
  • Rao SS, O’Neil J, Liberator CD et al. Inhibition of NOTCH signaling by γ secretase inhibitor engages the RB pathway and elicits cell cycle exit in T-cell acute lymphoblastic leukemia cells. Cancer Res.69(7), 3060–3068 (2009).
  • Gao D, Inuzuka H, Tseng A, Chin RY, Toker A, Wei W. Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APCCdh1-mediated Skp2 destruction. Nat. Cell. Biol.11(4), 397–408 (2009).
  • Lin HK, Wang G, Chen Z et al. Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB. Nat. Cell. Biol.11(4), 420–432 (2009).
  • Medema RH, Kops GJ, Bos JL, Burgering BM. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature404(6779), 782–787 (2000).
  • Sicinska E, Aifantis I, Le Cam L et al. Requirement for cyclin D3 in lymphocyte development and T cell leukemias. Cancer Cell4(6), 451–461 (2003).
  • Silva A, Laranjeira AB, Martins LR et al. IL-7 contributes to the progression of human T-cell acute lymphoblastic leukemias. Cancer Res.71(14), 4780–4789 (2011).
  • Barata JT, Silva A, Abecasis M, Carlesso N, Cumano A, Cardoso AA. Molecular and functional evidence for activity of murine IL-7 on human lymphocytes. Exp. Hematol.34(9), 1133–1142 (2006).
  • Scupoli MT, Vinante F, Krampera M et al. Thymic epithelial cells promote survival of human T-cell acute lymphoblastic leukemia blasts: the role of interleukin-7. Haematologica88(11), 1229–1237 (2003).
  • Scupoli MT, Perbellini O, Krampera M, Vinante F, Cioffi F, Pizzolo G. Interleukin 7 requirement for survival of T-cell acute lymphoblastic leukemia and human thymocytes on bone marrow stroma. Haematologica92(2), 264–266 (2007).
  • Cullion K, Draheim KM, Hermance N et al. Targeting the Notch1 and mTOR pathways in a mouse T-ALL model. Blood113(24), 6172–6181 (2009).
  • Silva A, Yunes JA, Cardoso BA et al. PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability. J. Clin. Invest.118(11), 3762–3774 (2008).
  • Silva A, Jotta PY, Silveira AB et al. Regulation of PTEN by CK2 and Notch1 in primary T-cell acute lymphoblastic leukemia: rationale for combined use of CK2- and γ-secretase inhibitors. Haematologica95(4), 674–678 (2010).
  • Martins LR, Lucio P, Silva MC et al. Targeting CK2 overexpression and hyperactivation as a novel therapeutic tool in chronic lymphocytic leukemia. Blood116(15), 2724–2731 (2010).
  • Real PJ, Tosello V, Palomero T et al. Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia. Nat. Med.15(1), 50–58 (2009).

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