Notch signaling as a therapeutic target for acute lymphoblastic leukemia

References

• Chiaretti S, Zini G, Bassan R. Diagnosis and subclassification of acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis. 2014;6(1):e2014073.
   PubMedGoogle Scholar
• Pui CH, Gajjar AJ, Kane JR, et al. Challenging issues in pediatric oncology. Nat Reviews Clin Oncology. 2011 Jun 28;8(9):540–549.
   PubMed Web of Science ®Google Scholar
• Pica A, Di Santi A, D’Angelo V, et al. Effect of rMnSOD on survival signaling in pediatric high risk T-cell acute lymphoblastic leukaemia. J Cell Physiol. 2015 May;230(5):1086–1093.
   PubMed Web of Science ®Google Scholar
• Weng AP, Ferrando AA, Lee W, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004 Oct 8;306(5694):269–271.
   PubMed Web of Science ®Google Scholar
• Bellavia D, Campese AF, Checquolo S, et al. Combined expression of pTalpha and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis. Proc Natl Acad Sci USA. 2002 Mar 19;99(6):3788–3793.
   PubMed Web of Science ®Google Scholar
• Bernasconi-Elias P, Hu T, Jenkins D, et al. Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies. Oncogene. 2016 Nov 24;35(47):6077–6086.
   PubMed Web of Science ®Google Scholar
• Takebe N, Miele L, Harris PJ, et al. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Reviews Clin Oncology. 2015 Aug;12(8):445–464.
   PubMed Web of Science ®Google Scholar
• 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. 2006 Jun;26(12):4642–4651.
   PubMed Web of Science ®Google Scholar
• Sulis ML, Williams O, Palomero T, et al. NOTCH1 extracellular juxtamembrane expansion mutations in T-ALL. Blood. 2008 Aug 1;112(3):733–740.
   PubMed Web of Science ®Google Scholar
• O’Neil J, Grim J, Strack P, et al. FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. J Exp Med. 2007 Aug 6;204(8):1813–1824.
   PubMed Web of Science ®Google Scholar
• Bellavia D, Campese AF, Alesse E, et al. Constitutive activation of NF-kappaB and T-cell leukemia/lymphoma in Notch3 transgenic mice. Embo J. 2000 Jul 3;19(13):3337–3348.
   PubMed Web of Science ®Google Scholar
• Campese AF, Bellavia D, Gulino A, et al. Notch signalling at the crossroads of T cell development and leukemogenesis. Semin Cell Dev Biol. 2003 Apr;14(2):151–157.
   PubMed Web of Science ®Google Scholar
• Felli MP, Vacca A, Calce A, et al. PKC theta mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia. Oncogene. 2005 Feb 3;24(6):992–1000.
   PubMed Web of Science ®Google Scholar
• Pelullo M, Quaranta R, Talora C, et al. Notch3/Jagged1 circuitry reinforces notch signaling and sustains T-ALL. Neoplasia. 2014 Dec;16(12):1007–1017.
   PubMed Web of Science ®Google Scholar
• Vacca A, Felli MP, Palermo R, et al. Notch3 and pre-TCR interaction unveils distinct NF-kappaB pathways in T-cell development and leukemia. Embo J. 2006 Mar 8;25(5):1000–1008.
   PubMed Web of Science ®Google Scholar
• Radojcic V, Maillard I. A jagged road to lymphoma aggressiveness. Cancer Cell. 2014 Mar 17;25(3):261–263.
   PubMed Web of Science ®Google Scholar
• Micci F, Panagopoulos I, Tjonnfjord GE, et al. Molecular cytogenetic characterization of t(14;19)(q32;p13), a new recurrent translocation in B cell malignancies. Virchows Archiv. 2007 May;450(5):559–565.
   PubMed Web of Science ®Google Scholar
• Kuang SQ, Fang Z, Zweidler-McKay PA, et al. Epigenetic inactivation of Notch-Hes pathway in human B-cell acute lymphoblastic leukemia. PloS One. 2013;8(4):e61807.
   PubMed Web of Science ®Google Scholar
• Zweidler-McKay PA, He Y, Xu L, et al. Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies. Blood. 2005 Dec 1;106(12):3898–3906.
   PubMed Web of Science ®Google Scholar
• Rosati E, Sabatini R, Rampino G, et al. Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells. Blood. 2009 Jan 22;113(4):856–865.
   PubMed Web of Science ®Google Scholar
• Martins VC, Busch K, Juraeva D, et al. Cell competition is a tumour suppressor mechanism in the thymus. Nature. 2014 May 22;509(7501):465–470.
   PubMed Web of Science ®Google Scholar
• Sanchez-Martin M, Ferrando A. The NOTCH1-MYC highway toward T-cell acute lymphoblastic leukemia. Blood. 2017 Mar 2;129(9):1124–1133.
   PubMed Web of Science ®Google Scholar
• Ultimo S, Martelli AM, Zauli G, et al. ROLES AND CLINICAL IMPLICATIONS OF MicroRNAs IN ACUTE LYMPHOBLASTIC LEUKEMIA. J Cell Physiol. 2017 Nov;20. First published: 28 February 2018 DOI: 10.1002/jcp.26290
   Google Scholar
• Chiarini F, Lonetti A, Evangelisti C, et al. Advances in understanding the acute lymphoblastic leukemia bone marrow microenvironment: from biology to therapeutic targeting. Biochim Biophys Acta. 2016 Mar;1863(3):449–463.
   PubMed Web of Science ®Google Scholar
• Randhawa S, Cho BS, Ghosh D, et al. Effects of pharmacological and genetic disruption of CXCR4 chemokine receptor function in B-cell acute lymphoblastic leukaemia. Br J Haematol. 2016 Aug;174(3):425–436.
   PubMed Web of Science ®Google Scholar
• Wang W, Zimmerman G, Huang X, et al. Aberrant Notch signaling in the bone marrow microenvironment of osteoblast-mediated support of acute lymphoid leukemia suppresses hematopoietic niche function. Cancer Res. 2016 Mar 15;76(6):1641–1652.
   PubMed Web of Science ®Google Scholar
• Nwabo Kamdje AH, Mosna F, Bifari F, et al. Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow-derived mesenchymal stromal cells. Blood. 2011 Jul 14;118(2):380–389.
   PubMed Web of Science ®Google Scholar
• Bhojwani D, Pui CH. Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 2013 May;14(6):e205–17.
   PubMed Web of Science ®Google Scholar
• Tatarek J, Cullion K, Ashworth T, et al. Notch1 inhibition targets the leukemia-initiating cells in a Tal1/Lmo2 mouse model of T-ALL. Blood. 2011 Aug 11;118(6):1579–1590.
   PubMed Web of Science ®Google Scholar
• Takebe N, Nguyen D, Yang SX. Targeting notch signaling pathway in cancer: clinical development advances and challenges. Pharmacol Ther. 2014 Feb;141(2):140–149.
   PubMed Web of Science ®Google Scholar
• Palomero T, Barnes KC, Real PJ, et al. CUTLL1, a novel human T-cell lymphoma cell line with t(7;9) rearrangement, aberrant NOTCH1 activation and high sensitivity to gamma-secretase inhibitors. Leukemia. 2006 Jul;20(7):1279–1287.
   PubMed Web of Science ®Google Scholar
• Rao SS, O’Neil J, Liberator CD, et al. Inhibition of NOTCH signaling by gamma secretase inhibitor engages the RB pathway and elicits cell cycle exit in T-cell acute lymphoblastic leukemia cells. Cancer Res. 2009 Apr 01;69(7):3060–3068.
   PubMed Web of Science ®Google Scholar
• Chiang MY, Wang Q, Gormley AC, et al. High selective pressure for Notch1 mutations that induce Myc in T-cell acute lymphoblastic leukemia. Blood. 2016 Nov 3;128(18):2229–2240.
   PubMed Web of Science ®Google Scholar
• van Es JH, van Gijn ME, Riccio O, et al. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature. 2005 Jun 16;435(7044):959–963.
   PubMed Web of Science ®Google Scholar
• Papayannidis C, DeAngelo DJ, Stock W, et al. A Phase 1 study of the novel gamma-secretase inhibitor PF-03084014 in patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Blood Cancer J. 2015 Sep 25;5:e350.
   PubMed Web of Science ®Google Scholar
• Paganin M, Ferrando A. Molecular pathogenesis and targeted therapies for NOTCH1-induced T-cell acute lymphoblastic leukemia. Blood Rev. 2011 Mar;25(2):83–90.
   PubMed Web of Science ®Google Scholar
• Ran Y, Hossain F, Pannuti A, et al. gamma-Secretase inhibitors in cancer clinical trials are pharmacologically and functionally distinct. EMBO Mol Med. 2017 Jul;9(7):950–966.
   PubMed Web of Science ®Google Scholar
• Wu Y, Cain-Hom C, Choy L, et al. Therapeutic antibody targeting of individual Notch receptors. Nature. 2010 Apr 15;464(7291):1052–1057.
   PubMed Web of Science ®Google Scholar
• Aste-Amezaga M, Zhang N, Lineberger JE, et al. Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors. PloS One. 2010 Feb 8;5(2):e9094.
   PubMed Web of Science ®Google Scholar
• Agnusdei V, Minuzzo S, Frasson C, et al. Therapeutic antibody targeting of Notch1 in T-acute lymphoblastic leukemia xenografts. Leukemia. 2014 Feb;28(2):278–288.
   PubMed Web of Science ®Google Scholar
• Li K, Li Y, Wu W, et al. Modulation of Notch signaling by antibodies specific for the extracellular negative regulatory region of NOTCH3. J Biol Chem. 2008 Mar 21;283(12):8046–8054.
   PubMed Web of Science ®Google Scholar
• Yen WC, Fischer MM, Axelrod F, et al. Targeting Notch signaling with a Notch2/Notch3 antagonist (tarextumab) inhibits tumor growth and decreases tumor-initiating cell frequency. Clin Cancer Res. 2015 May 1;21(9):2084–2095.
   PubMed Web of Science ®Google Scholar
• Minuzzo S, Agnusdei V, Pusceddu I, et al. DLL4 regulates NOTCH signaling and growth of T acute lymphoblastic leukemia cells in NOD/SCID mice. Carcinogenesis. 2015 Jan;36(1):115–121.
   PubMed Web of Science ®Google Scholar
• Hayashi H, Nakagami H, Takeichi M, et al. HIG1, a novel regulator of mitochondrial gamma-secretase, maintains normal mitochondrial function. Faseb J. 2012 Jun;26(6):2306–2317.
   PubMed Web of Science ®Google Scholar
• Palermo R, Checquolo S, Bellavia D, et al. The molecular basis of notch signaling regulation: a complex simplicity. Curr Mol Med. 2014 Jan;14(1):34–44.
   PubMed Web of Science ®Google Scholar
• Chemaly ER, Troncone L, Lebeche D. SERCA control of cell death and survival. Cell Calcium. 2018 Jan;69:46-61. doi: 10.1016/j.ceca.2017.07.001. Epub 2017 Jul 12.
   Google Scholar
• Roti G, Carlton A, Ross KN, et al. Complementary genomic screens identify SERCA as a therapeutic target in NOTCH1 mutated cancer. Cancer Cell. 2013 Mar 18;23(3):390–405.
   PubMed Web of Science ®Google Scholar
• De Ford C, Heidersdorf B, Haun F, et al. The clerodane diterpene casearin J induces apoptosis of T-ALL cells through SERCA inhibition, oxidative stress, and interference with Notch1 signaling. Cell Death Dis. 2016 Jan 28;7:e2070.
   PubMed Web of Science ®Google Scholar
• Sun Y, St Clair DK, Xu Y, et al. A NADPH oxidase-dependent redox signaling pathway mediates the selective radiosensitization effect of parthenolide in prostate cancer cells. Cancer Res. 2010 Apr 1;70(7):2880–2890.
   PubMed Web of Science ®Google Scholar
• Roti G, Qi J, Kitara S, et al. Leukemia-specific delivery of mutant NOTCH1 targeted therapy. J Exp Med. 2018 Jan 2;215(1):197-216. doi: 10.1084/jem.20151778. Epub 2017 Nov 20.
   Google Scholar
• Thompson BJ, Buonamici S, Sulis ML, et al. The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J Exp Med. 2007 Aug 6;204(8):1825–1835.
   PubMed Web of Science ®Google Scholar
• Guarani V, Deflorian G, Franco CA, et al. Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase. Nature. 2011 May 12;473(7346):234–238.
   PubMed Web of Science ®Google Scholar
• Palermo R, Checquolo S, Giovenco A, et al. Acetylation controls Notch3 stability and function in T-cell leukemia. Oncogene. 2012 Aug 16;31(33):3807–3817.
   PubMed Web of Science ®Google Scholar
• Checquolo S, Palermo R, Cialfi S, et al. Differential subcellular localization regulates c-Cbl E3 ligase activity upon Notch3 protein in T-cell leukemia. Oncogene. 2010 Mar 11;29(10):1463–1474.
   PubMed Web of Science ®Google Scholar
• Franciosa G, Diluvio G, Gaudio FD, et al. Prolyl-isomerase Pin1 controls Notch3 protein expression and regulates T-ALL progression. Oncogene. 2016 Sep 8;35(36):4741–4751.
   PubMed Web of Science ®Google Scholar
• Zhou XZ, Lu KP. The isomerase PIN1 controls numerous cancer-driving pathways and is a unique drug target. Nat Rev Cancer. 2016 Jul;16(7):463–478.
   PubMed Web of Science ®Google Scholar
• Yatim A, Benne C, Sobhian B, et al. NOTCH1 nuclear interactome reveals key regulators of its transcriptional activity and oncogenic function. Mol Cell. 2012 Nov 09;48(3):445–458.
   PubMed Web of Science ®Google Scholar
• Rustighi A, Zannini A, Tiberi L, et al. Prolyl-isomerase Pin1 controls normal and cancer stem cells of the breast. EMBO Mol Med. 2014 Jan;6(1):99–119.
   PubMed Web of Science ®Google Scholar
• Fan G, Fan Y, Gupta N, et al. Peptidyl-prolyl isomerase Pin1 markedly enhances the oncogenic activity of the rel proteins in the nuclear factor-kappaB family. Cancer Res. 2009 Jun 1;69(11):4589–4597.
   PubMed Web of Science ®Google Scholar
• Kumar V, Palermo R, Talora C, et al. Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia. Leukemia. 2014 Dec;28(12):2324–2335.
   PubMed Web of Science ®Google Scholar
• Wei S, Kozono S, Kats L, et al. Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer. Nat Med. 2015 May;21(5):457–466.
   PubMed Web of Science ®Google Scholar
• Rustighi A, Zannini A, Campaner E, et al. PIN1 in breast development and cancer: a clinical perspective. Cell Death Differ. 2017 Feb;24(2):200–211.
   PubMed Web of Science ®Google Scholar
• Zampieri M, Ciccarone F, Palermo R, et al. The epigenetic factor BORIS/CTCFL regulates the NOTCH3 gene expression in cancer cells. Biochim Biophys Acta. 2014 Sep;1839(9):813–825.
   PubMedGoogle Scholar
• Schwanbeck R. The role of epigenetic mechanisms in Notch signaling during development. J Cell Physiol. 2015 May;230(5):969–981.
   PubMed Web of Science ®Google Scholar
• Oswald F, Tauber B, Dobner T, et al. p300 acts as a transcriptional coactivator for mammalian Notch-1. Mol Cell Biol. 2001 Nov;21(22):7761–7774.
   PubMed Web of Science ®Google Scholar
• Kurooka H, Honjo T. Functional interaction between the mouse notch1 intracellular region and histone acetyltransferases PCAF and GCN5. J Biol Chem. 2000 Jun 02;275(22):17211–17220.
   PubMed Web of Science ®Google Scholar
• Wang H, Zang C, Taing L, et al. NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers. Proc Natl Acad Sci USA. 2014 Jan 14;111(2):705–710.
   PubMed Web of Science ®Google Scholar
• Choi SH, Severson E, Pear WS, et al. The common oncogenomic program of NOTCH1 and NOTCH3 signaling in T-cell acute lymphoblastic leukemia. PloS One. 2017;12(10):e0185762.
   PubMed Web of Science ®Google Scholar
• Ntziachristos P, Tsirigos A, Van Vlierberghe P, et al. Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia. Nat Med. 2012 Feb 06;18(2):298–301.
   PubMed Web of Science ®Google Scholar
• Ntziachristos P, Tsirigos A, Welstead GG, et al. Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. Nature. 2014 Oct 23;514(7523):513–517.
   PubMed Web of Science ®Google Scholar
• Ohtaka M, Itoh M, Tohda S. BMI1 inhibitors down-regulate NOTCH signaling and suppress proliferation of acute leukemia cells. Anticancer Res. 2017 Nov;37(11):6047–6053.
   PubMed Web of Science ®Google Scholar
• Zhou B, Wang S, Mayr C, et al. miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely. Proc Natl Acad Sci USA. 2007 Apr 24;104(17):7080–7085.
   PubMed Web of Science ®Google Scholar
• Ghisi M, Corradin A, Basso K, et al. Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150. Blood. 2011 Jun 30;117(26):7053–7062.
   PubMed Web of Science ®Google Scholar
• Qian L, Zhang W, Lei B, et al. MicroRNA-101 regulates T-cell acute lymphoblastic leukemia progression and chemotherapeutic sensitivity by targeting Notch1. Oncol Rep. 2016 Nov;36(5):2511–2516.
   PubMed Web of Science ®Google Scholar
• Ortega M, Bhatnagar H, Lin AP, et al. A microRNA-mediated regulatory loop modulates NOTCH and MYC oncogenic signals in B- and T-cell malignancies. Leukemia. 2015 Apr;29(4):968–976.
   PubMed Web of Science ®Google Scholar
• Mavrakis KJ, Wolfe AL, Oricchio E, et al. Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia. Nat Cell Biol. 2010 Apr;12(4):372–379.
   PubMed Web of Science ®Google Scholar
• Fragoso R, Mao T, Wang S, et al. Modulating the strength and threshold of NOTCH oncogenic signals by mir-181a-1/b-1. PLoS Genet. 2012;8(8):e1002855.
   PubMed Web of Science ®Google Scholar
• Real PJ, Tosello V, Palomero T, et al. Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia. Nat Med. 2009 Jan;15(1):50–58.
   PubMed Web of Science ®Google Scholar
• Zheng H, Pritchard DM, Yang X, et al. KLF4 gene expression is inhibited by the notch signaling pathway that controls goblet cell differentiation in mouse gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G490–8.
   PubMed Web of Science ®Google Scholar
• Samon JB, Castillo-Martin M, Hadler M, et al. Preclinical analysis of the gamma-secretase inhibitor PF-03084014 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia. Mol Cancer Ther. 2012 Jul;11(7):1565–1575.
   PubMed Web of Science ®Google Scholar
• Cullion K, Draheim KM, Hermance N, et al. Targeting the Notch1 and mTOR pathways in a mouse T-ALL model. Blood. 2009 Jun 11;113(24):6172–6181.
   PubMed Web of Science ®Google Scholar
• Shepherd C, Banerjee L, Cheung CW, et al. PI3K/mTOR inhibition upregulates NOTCH-MYC signalling leading to an impaired cytotoxic response. Leukemia. 2013 Mar;27(3):650–660.
   PubMed Web of Science ®Google Scholar
• Vilimas T, Mascarenhas J, Palomero T, et al. Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia. Nat Med. 2007 Jan;13(1):70–77.
   PubMed Web of Science ®Google Scholar
• Knoechel B, Roderick JE, Williamson KE, et al. An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia. Nat Genet. 2014 Apr;46(4):364–370.
   PubMed Web of Science ®Google Scholar
• Sanchez-Martin M, Ambesi-Impiombato A, Qin Y, et al. Synergistic antileukemic therapies in NOTCH1-induced T-ALL. Proc Natl Acad Sci USA. 2017 Feb 21;114(8):2006–2011.
   PubMed Web of Science ®Google Scholar
• Gutierrez A, Pan L, Groen RW, et al. Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia. J Clin Invest. 2014 Feb;124(2):644–655.
   PubMed Web of Science ®Google Scholar
• Espinoza I, Miele L. Notch inhibitors for cancer treatment. Pharmacol Ther. 2013 Aug;139(2):95–110.
   PubMed Web of Science ®Google Scholar
• Kawahara T, Kawaguchi-Ihara N, Okuhashi Y, et al. Cyclopamine and quercetin suppress the growth of leukemia and lymphoma cells. Anticancer Res. 2009 Nov;29(11):4629–4632.
   PubMed Web of Science ®Google Scholar
• Mori M, Tottone L, Quaglio D, et al. Identification of a novel chalcone derivative that inhibits Notch signaling in T-cell acute lymphoblastic leukemia. Sci Rep. 2017 May 19;7(1):2213.
   PubMedGoogle Scholar
• Moellering RE, Cornejo M, Davis TN, et al. Direct inhibition of the NOTCH transcription factor complex. Nature. 2009 Nov 12;462(7270):182–188.
   PubMed Web of Science ®Google Scholar
• Cox CV, Diamanti P, Evely RS, et al. Expression of CD133 on leukemia-initiating cells in childhood ALL. Blood. 2009 Apr 2;113(14):3287–3296.
   PubMed Web of Science ®Google Scholar
• Mohle R, Schittenhelm M, Failenschmid C, et al. Functional response of leukaemic blasts to stromal cell-derived factor-1 correlates with preferential expression of the chemokine receptor CXCR4 in acute myelomonocytic and lymphoblastic leukaemia. Br J Haematol. 2000 Sep;110(3):563–572.
   PubMed Web of Science ®Google Scholar
• Rombouts EJ, Pavic B, Lowenberg B, et al. Relation between CXCR-4 expression, Flt3 mutations, and unfavorable prognosis of adult acute myeloid leukemia. Blood. 2004 Jul 15;104(2):550–557.
   PubMed Web of Science ®Google Scholar
• Passaro D, Irigoyen M, Catherinet C, et al. CXCR4 is required for leukemia-initiating cell activity in T cell acute lymphoblastic leukemia. Cancer Cell. 2015 Jun 8;27(6):769–779.
   PubMed Web of Science ®Google Scholar
• Pitt LA, Tikhonova AN, Hu H, et al. CXCL12-producing vascular endothelial niches control acute T cell leukemia maintenance. Cancer Cell. 2015 Jun 8;27(6):755–768.
   PubMed Web of Science ®Google Scholar
• Meng W, Xue S, Chen Y. The role of CXCL12 in tumor microenvironment. Gene. 2018 Jan 30;641:105–110.
   PubMed Web of Science ®Google Scholar
• Zou L, Barnett B, Safah H, et al. Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Cancer Res. 2004 Nov 15;64(22):8451–8455.
   PubMed Web of Science ®Google Scholar
• Barbarulo A, Grazioli P, Campese AF, et al. Notch3 and canonical NF-kappaB signaling pathways cooperatively regulate Foxp3 transcription. J Immunology. 2011 Jun 1;186(11):6199–6206.
   PubMed Web of Science ®Google Scholar
• Grazioli P, Felli MP, Screpanti I, et al. The mazy case of Notch and immunoregulatory cells. J Leukoc Biol. 2017 Aug;102(2):361–368.
   PubMed Web of Science ®Google Scholar
• Domanska UM, Kruizinga RC, Nagengast WB, et al. A review on CXCR4/CXCL12 axis in oncology: no place to hide. Eur J Cancer. 2013 Jan;49(1):219–230.
   PubMed Web of Science ®Google Scholar
• Juarez J, Dela Pena A, Baraz R, et al. CXCR4 antagonists mobilize childhood acute lymphoblastic leukemia cells into the peripheral blood and inhibit engraftment. Leukemia. 2007 Jun;21(6):1249–1257.
   PubMed Web of Science ®Google Scholar
• Scala S. Molecular pathways: targeting the CXCR4-CXCL12 axis–untapped potential in the tumor microenvironment. Clin Cancer Res. 2015 Oct 1; 21(19):4278–4285.
   PubMed Web of Science ®Google Scholar
• Beider K, Darash-Yahana M, Blaier O, et al. Combination of imatinib with CXCR4 antagonist BKT140 overcomes the protective effect of stroma and targets CML in vitro and in vivo. Mol Cancer Ther. 2014 May;13(5):1155–1169.
   PubMed Web of Science ®Google Scholar
• Walenkamp AME, Lapa C, Herrmann K, et al. CXCR4 ligands: the next big hit? J Nucl Med. 2017 Sep;58(Suppl 2):77S–82S.
   PubMedGoogle Scholar