International Journal of Hematology

, Volume 107, Issue 5, pp 502–512 | Cite as

Targeting autophagy in lymphomas: a double-edged sword?

Review Article
  • 153 Downloads

Abstract

Autophagy (also known as macroautophagy) is a lysosomal degradation pathway for the clearance of cellular materials, which manifests as an adaptive response to stress stimuli. Over the past decade, numerous studies have linked autophagy with cancer initiation, progression, and chemoresistance. Autophagy defects in normal cells facilitate tumorigenesis; paradoxically, enhanced autophagy allows prolonged survival in cancer cells upon nutrient shortage, low oxygen, or chemotherapies. However, the mechanism underlying the switch from the cytoprotective role of autophagy to autophagic cell death remains incompletely understood. Here, I review the latest advances in understanding the role of autophagy in lymphomas, current challenges, and future directions.

Keywords

Autophagy Lymphoma Cell survival Cell death Chemotherapy 

Notes

Compliance with ethical standards

Conflict of interest

The author has nothing to disclose.

References

  1. 1.
    De Duve C, Pressman BC, Gianetto R, Wattiaux R, Appelmans F. Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J. 1955;60(4):604–17.PubMedCentralGoogle Scholar
  2. 2.
    Klionsky DJ. Autophagy revisited: a conversation with Christian de Duve. Autophagy. 2008;4(6):740–3.PubMedGoogle Scholar
  3. 3.
    Novikoff AB, Beaufay H, De Duve C. Electron microscopy of lysosomerich fractions from rat liver. J Biophys Biochem Cytol. 1956;2(4 Suppl):179–84.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Ashford TP, Porter KR. Cytoplasmic components in hepatic cell lysosomes. J Cell Biol. 1962;12:198–202.PubMedPubMedCentralGoogle Scholar
  5. 5.
    de Duve C. The lysosome turns fifty. Nat Cell Biol. 2005;7(9):847–9.PubMedGoogle Scholar
  6. 6.
    De Duve C, Wattiaux R. Functions of lysosomes. Annu Rev Physiol. 1966;28:435–92.PubMedGoogle Scholar
  7. 7.
    Takeshige K, Baba M, Tsuboi S, Noda T, Ohsumi Y. Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol. 1992;119(2):301–11.PubMedGoogle Scholar
  8. 8.
    Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993;333(1–2):169–74.PubMedGoogle Scholar
  9. 9.
    Titorenko VI, Keizer I, Harder W, Veenhuis M. Isolation and characterization of mutants impaired in the selective degradation of peroxisomes in the yeast Hansenula polymorpha. J Bacteriol. 1995;177(2):357–63.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Yuan W, Tuttle DL, Shi YJ, Ralph GS, Dunn WA Jr. Glucose-induced microautophagy in Pichia pastoris requires the alpha-subunit of phosphofructokinase. J Cell Sci. 1997;110(Pt 16):1935–45.PubMedGoogle Scholar
  11. 11.
    Yuan W, Stromhaug PE, Dunn WA Jr. Glucose-induced autophagy of peroxisomes in Pichia pastoris requires a unique E1-like protein. Mol Biol Cell. 1999;10(5):1353–66.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Mukaiyama H, Oku M, Baba M, Samizo T, Hammond AT, Glick BS, et al. Paz2 and 13 other PAZ gene products regulate vacuolar engulfment of peroxisomes during micropexophagy. Genes Cells. 2002;7(1):75–90.PubMedGoogle Scholar
  13. 13.
    Mizushima N. Noboru Mizushima: all about autophagy. Interview by Caitlin Sedwick. J Cell Biol. 2010;190(6):946–7.PubMedGoogle Scholar
  14. 14.
    Mizushima N, Sugita H, Yoshimori T, Ohsumi Y. A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy. J Biol Chem. 1998;273(51):33889–92.PubMedGoogle Scholar
  15. 15.
    Mizushima N, Kuma A, Kobayashi Y, Yamamoto A, Matsubae M, Takao T, et al. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. J Cell Sci. 2003;116(Pt 9):1679–88.PubMedGoogle Scholar
  16. 16.
    Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000;19(21):5720–8.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Mizushima N, Yamamoto A, Hatano M, Kobayashi Y, Kabeya Y, Suzuki K, et al. Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. J Cell Biol. 2001;152(4):657–68.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, et al. The role of autophagy during the early neonatal starvation period. Nature. 2004;432(7020):1032–6.PubMedGoogle Scholar
  19. 19.
    Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell. 2004;15(3):1101–11.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Melendez A, Levine B. Autophagy in C. elegans. WormBook. 2009;1–26.Google Scholar
  21. 21.
    Hanaoka H, Noda T, Shirano Y, Kato T, Hayashi H, Shibata D, et al. Leaf senescence and starvation-induced chlorosis are accelerated by the disruption of an Arabidopsis autophagy gene. Plant Physiol. 2002;129(3):1181–93.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Doelling JH, Walker JM, Friedman EM, Thompson AR, Vierstra RD. The APG8/12-activating enzyme APG7 is required for proper nutrient recycling and senescence in Arabidopsis thaliana. J Biol Chem. 2002;277(36):33105–14.PubMedGoogle Scholar
  23. 23.
    Lorincz P, Mauvezin C, Juhasz G. Exploring autophagy in Drosophila. Cells. 2017;6(3):22.PubMedCentralGoogle Scholar
  24. 24.
    Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006;441(7095):885–9.PubMedGoogle Scholar
  25. 25.
    Komatsu M, Waguri S, Koike M, Sou YS, Ueno T, Hara T, et al. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell. 2007;131(6):1149–63.PubMedGoogle Scholar
  26. 26.
    Tsukamoto S, Kuma A, Murakami M, Kishi C, Yamamoto A, Mizushima N. Autophagy is essential for preimplantation development of mouse embryos. Science. 2008;321(5885):117–20.PubMedGoogle Scholar
  27. 27.
    Mizushima N, Levine B. Autophagy in mammalian development and differentiation. Nat Cell Biol. 2010;12(9):823–30.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature. 2011;469(7330):323–35.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Jiang P, Mizushima N. Autophagy and human diseases. Cell Res. 2014;24(1):69–79.PubMedGoogle Scholar
  30. 30.
    Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147(4):728–41.PubMedGoogle Scholar
  31. 31.
    Harris J. Autophagy and cytokines. Cytokine. 2011;56(2):140–4.PubMedGoogle Scholar
  32. 32.
    Kongara S, Karantza V. The interplay between autophagy and ROS in tumorigenesis. Front Oncol. 2012;2:171.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Li L, Ishdorj G, Gibson SB. Reactive oxygen species regulation of autophagy in cancer: implications for cancer treatment. Free Radic Biol Med. 2012;53(7):1399–410.PubMedGoogle Scholar
  34. 34.
    Chen Z, Teo AE, McCarty N. ROS-induced CXCR4 signaling regulates mantle cell lymphoma (MCL) cell survival and drug resistance in the bone marrow microenvironment via autophagy. Clin Cancer Res. 2016;22(1):187–99.PubMedGoogle Scholar
  35. 35.
    Sui X, Chen R, Wang Z, Huang Z, Kong N, Zhang M, et al. Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment. Cell Death Dis. 2013;4:e838.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Zhang H, Chen Z, Miranda RN, Medeiros LJ, McCarty N. TG2 and NF-kappaB signaling coordinates the survival of mantle cell lymphoma cells via IL6-mediated autophagy. Cancer Res. 2016;76(21):6410–23.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Zhang H, McCarty N. Tampering with cancer chemoresistance by targeting the TGM2-IL6-autophagy regulatory network. Autophagy. 2017;13(3):627–8.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Colombo MI. Autophagy: a pathogen driven process. IUBMB Life. 2007;59(4–5):238–42.PubMedGoogle Scholar
  39. 39.
    Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999;402(6762):672–6.PubMedGoogle Scholar
  40. 40.
    Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003;112(12):1809–20.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Yue Z, Jin S, Yang C, Levine AJ, Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA. 2003;100(25):15077–82.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Chen Y, Lu Y, Lu C, Zhang L. Beclin-1 expression is a predictor of clinical outcome in patients with esophageal squamous cell carcinoma and correlated to hypoxia-inducible factor (HIF)-1alpha expression. Pathol Oncol Res. 2009;15(3):487–93.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Ding ZB, Shi YH, Zhou J, Qiu SJ, Xu Y, Dai Z, et al. Association of autophagy defect with a malignant phenotype and poor prognosis of hepatocellular carcinoma. Cancer Res. 2008;68(22):9167–75.PubMedGoogle Scholar
  44. 44.
    Pirtoli L, Cevenini G, Tini P, Vannini M, Oliveri G, Marsili S, et al. The prognostic role of Beclin 1 protein expression in high-grade gliomas. Autophagy. 2009;5(7):930–6.PubMedGoogle Scholar
  45. 45.
    Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C, Waguri S, et al. Autophagy-deficient mice develop multiple liver tumors. Genes Dev. 2011;25(8):795–800.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, Pellegatti P, et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science. 2011;334(6062):1573–7.PubMedGoogle Scholar
  47. 47.
    Janku F, McConkey DJ, Hong DS, Kurzrock R. Autophagy as a target for anticancer therapy. Nat Rev Clin Oncol. 2011;8(9):528–39.PubMedGoogle Scholar
  48. 48.
    Arsham AM, Howell JJ, Simon MC. A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets. J Biol Chem. 2003;278(32):29655–60.PubMedGoogle Scholar
  49. 49.
    Pouyssegur J, Dayan F, Mazure NM. Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature. 2006;441(7092):437–43.PubMedGoogle Scholar
  50. 50.
    Lum JJ, Bauer DE, Kong M, Harris MH, Li C, Lindsten T, et al. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell. 2005;120(2):237–48.PubMedGoogle Scholar
  51. 51.
    Yoshioka A, Miyata H, Doki Y, Yamasaki M, Sohma I, Gotoh K, et al. LC3, an autophagosome marker, is highly expressed in gastrointestinal cancers. Int J Oncol. 2008;33(3):461–8.PubMedGoogle Scholar
  52. 52.
    Lazova R, Klump V, Pawelek J. Autophagy in cutaneous malignant melanoma. J Cutan Pathol. 2010;37(2):256–68.PubMedGoogle Scholar
  53. 53.
    Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 2011;25(7):717–29.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Rosich L, Xargay-Torrent S, Lopez-Guerra M, Campo E, Colomer D, Roue G. Counteracting autophagy overcomes resistance to everolimus in mantle cell lymphoma. Clin Cancer Res. 2012;18(19):5278–89.PubMedGoogle Scholar
  55. 55.
    Rosich L, Colomer D, Roue G. Autophagy controls everolimus (RAD001) activity in mantle cell lymphoma. Autophagy. 2013;9(1):115–7.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Mathew R, Karantza-Wadsworth V, White E. Role of autophagy in cancer. Nat Rev Cancer. 2007;7(12):961–7.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Calabretta B, Salomoni P. Inhibition of autophagy: a new strategy to enhance sensitivity of chronic myeloid leukemia stem cells to tyrosine kinase inhibitors. Leuk Lymphoma. 2011;52(Suppl 1):54–9.PubMedGoogle Scholar
  58. 58.
    Watson AS, Mortensen M, Simon AK. Autophagy in the pathogenesis of myelodysplastic syndrome and acute myeloid leukemia. Cell Cycle. 2011;10(11):1719–25.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Helgason GV, Karvela M, Holyoake TL. Kill one bird with two stones: potential efficacy of BCR-ABL and autophagy inhibition in CML. Blood. 2011;118(8):2035–43.PubMedGoogle Scholar
  60. 60.
    Ekiz HA, Can G, Baran Y. Role of autophagy in the progression and suppression of leukemias. Crit Rev Oncol Hematol. 2012;81(3):275–85.PubMedGoogle Scholar
  61. 61.
    Sehgal AR, Konig H, Johnson DE, Tang D, Amaravadi RK, Boyiadzis M, et al. You eat what you are: autophagy inhibition as a therapeutic strategy in leukemia. Leukemia. 2015;29(3):517–25.PubMedGoogle Scholar
  62. 62.
    Auberger P, Puissant A. Autophagy, a key mechanism of oncogenesis and resistance in leukemia. Blood. 2017;129(5):547–52.PubMedGoogle Scholar
  63. 63.
    Sehn LH, Gascoyne RD. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 2015;125(1):22–32.PubMedGoogle Scholar
  64. 64.
    Friedberg JW. How I treat double-hit lymphoma. Blood. 2017;130(5):590–6.PubMedGoogle Scholar
  65. 65.
    Reed JC. Bcl-2-family proteins and hematologic malignancies: history and future prospects. Blood. 2008;111(7):3322–30.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB, et al. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 2004;6(12):1221–8.PubMedGoogle Scholar
  67. 67.
    Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005;122(6):927–39.PubMedGoogle Scholar
  68. 68.
    Brem EA, Thudium K, Khubchandani S, Tsai PC, Olejniczak SH, Bhat S, et al. Distinct cellular and therapeutic effects of obatoclax in rituximab-sensitive and -resistant lymphomas. Br J Haematol. 2011;153(5):599–611.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Nicotra G, Mercalli F, Peracchio C, Castino R, Follo C, Valente G, et al. Autophagy-active beclin-1 correlates with favourable clinical outcome in non-Hodgkin lymphomas. Mod Pathol. 2010;23(7):937–50.PubMedGoogle Scholar
  70. 70.
    Huang JJ, Zhu YJ, Lin TY, Jiang WQ, Huang HQ, Li ZM. Beclin 1 expression predicts favorable clinical outcome in patients with diffuse large B-cell lymphoma treated with R-CHOP. Hum Pathol. 2011;42(10):1459–66.PubMedGoogle Scholar
  71. 71.
    Rohatgi RA, Shaw LM. An autophagy-independent function for Beclin 1 in cancer. Mol Cell Oncol. 2016;3(1):e1030539.PubMedGoogle Scholar
  72. 72.
    Xu F, Fang Y, Yan L, Xu L, Zhang S, Cao Y, et al. Nuclear localization of Beclin 1 promotes radiation-induced DNA damage repair independent of autophagy. Sci Rep. 2017;7:45385.PubMedPubMedCentralGoogle Scholar
  73. 73.
    McCarthy A, Marzec J, Clear A, Petty RD, Coutinho R, Matthews J, et al. Dysregulation of autophagy in human follicular lymphoma is independent of overexpression of BCL-2. Oncotarget. 2014;5(22):11653–68.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Moreau P, Attal M, Facon T. Frontline therapy of multiple myeloma. Blood. 2015;125(20):3076–84.PubMedGoogle Scholar
  75. 75.
    Campo E, Rule S. Mantle cell lymphoma: evolving management strategies. Blood. 2015;125(1):48–55.PubMedGoogle Scholar
  76. 76.
    Jia L, Gopinathan G, Sukumar JT, Gribben JG. Blocking autophagy prevents bortezomib-induced NF-kappaB activation by reducing I-kappaBalpha degradation in lymphoma cells. PLoS One. 2012;7(2):e32584.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Korolchuk VI, Mansilla A, Menzies FM, Rubinsztein DC. Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates. Mol Cell. 2009;33(4):517–27.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Bhalla S, Evens AM, Prachand S, Schumacker PT, Gordon LI. Paradoxical regulation of hypoxia inducible factor-1alpha (HIF-1alpha) by histone deacetylase inhibitor in diffuse large B-cell lymphoma. PLoS One. 2013;8(11):e81333.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Zang C, Eucker J, Liu H, Coordes A, Lenarz M, Possinger K, et al. Inhibition of pan-class I phosphatidyl-inositol-3-kinase by NVP-BKM120 effectively blocks proliferation and induces cell death in diffuse large B-cell lymphoma. Leuk Lymphoma. 2014;55(2):425–34.PubMedGoogle Scholar
  80. 80.
    Yuan H, He M, Cheng F, Bai R, da Silva SR, Aguiar RC, et al. Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy. Oncotarget. 2017;8(9):14912–24.PubMedPubMedCentralGoogle Scholar
  81. 81.
    Inamdar AA, Goy A, Ayoub NM, Attia C, Oton L, Taruvai V, et al. Mantle cell lymphoma in the era of precision medicine-diagnosis, biomarkers and therapeutic agents. Oncotarget. 2016;7(30):48692–731.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Tucker D, Rule S. Novel agents in mantle cell lymphoma. Expert Rev Anticancer Ther. 2017;17(6):491–506.PubMedGoogle Scholar
  83. 83.
    Gera JF, Mellinghoff IK, Shi Y, Rettig MB, Tran C, Hsu JH, et al. AKT activity determines sensitivity to mammalian target of rapamycin (mTOR) inhibitors by regulating cyclin D1 and c-myc expression. J Biol Chem. 2004;279(4):2737–46.PubMedGoogle Scholar
  84. 84.
    Dal Col J, Dolcetti R. GSK-3beta inhibition: at the crossroad between Akt and mTOR constitutive activation to enhance cyclin D1 protein stability in mantle cell lymphoma. Cell Cycle. 2008;7(18):2813–6.Google Scholar
  85. 85.
    Averous J, Fonseca BD, Proud CG. Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1. Oncogene. 2008;27(8):1106–13.PubMedGoogle Scholar
  86. 86.
    Easton JB, Houghton PJ. mTOR and cancer therapy. Oncogene. 2006;25(48):6436–46.PubMedGoogle Scholar
  87. 87.
    Hipp S, Ringshausen I, Oelsner M, Bogner C, Peschel C, Decker T. Inhibition of the mammalian target of rapamycin and the induction of cell cycle arrest in mantle cell lymphoma cells. Haematologica. 2005;90(10):1433–4.PubMedGoogle Scholar
  88. 88.
    Dal Col J, Zancai P, Terrin L, Guidoboni M, Ponzoni M, Pavan A, et al. Distinct functional significance of Akt and mTOR constitutive activation in mantle cell lymphoma. Blood. 2008;111(10):5142–51.Google Scholar
  89. 89.
    Yazbeck VY, Buglio D, Georgakis GV, Li Y, Iwado E, Romaguera JE, et al. Temsirolimus downregulates p21 without altering cyclin D1 expression and induces autophagy and synergizes with vorinostat in mantle cell lymphoma. Exp Hematol. 2008;36(4):443–50.PubMedGoogle Scholar
  90. 90.
    Cagnol S, Chambard JC. ERK and cell death: mechanisms of ERK-induced cell death–apoptosis, autophagy and senescence. FEBS J. 2010;277(1):2–21.PubMedGoogle Scholar
  91. 91.
    Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F, Erdin S, et al. TFEB links autophagy to lysosomal biogenesis. Science. 2011;332(6036):1429–33.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Sivaprasad U, Basu A. Inhibition of ERK attenuates autophagy and potentiates tumour necrosis factor-alpha-induced cell death in MCF-7 cells. J Cell Mol Med. 2008;12(4):1265–71.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Martinez-Lopez N, Athonvarangkul D, Mishall P, Sahu S, Singh R. Autophagy proteins regulate ERK phosphorylation. Nat Commun. 2013;4:2799.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Martinez-Lopez N, Singh R. ATGs: scaffolds for MAPK/ERK signaling. Autophagy. 2014;10(3):535–7.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Dupere-Richer D, Kinal M, Menasche V, Nielsen TH, Del Rincon S, Pettersson F, et al. Vorinostat-induced autophagy switches from a death-promoting to a cytoprotective signal to drive acquired resistance. Cell Death Dis. 2013;4:e486.PubMedPubMedCentralGoogle Scholar
  96. 96.
    Torgersen ML, Engedal N, Boe SO, Hokland P, Simonsen A. Targeting autophagy potentiates the apoptotic effect of histone deacetylase inhibitors in t(8;21) AML cells. Blood. 2013;122(14):2467–76.PubMedGoogle Scholar
  97. 97.
    Alinari L, Mahoney E, Patton J, Zhang X, Huynh L, Earl CT, et al. FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death. Blood. 2011;118(26):6893–903.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Alinari L, Baiocchi RA, Praetorius-Ibba M. FTY720-induced blockage of autophagy enhances anticancer efficacy of milatuzumab in mantle cell lymphoma: is FTY720 the next autophagy-blocking agent in lymphoma treatment? Autophagy. 2012;8(3):416–7.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Xiao Y, Guan J. 17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression. Neoplasma. 2015;62(3):391–7.PubMedGoogle Scholar
  100. 100.
    Mastorci K, Montico B, Fae DA, Sigalotti L, Ponzoni M, Inghirami G, et al. Phospholipid scramblase 1 as a critical node at the crossroad between autophagy and apoptosis in mantle cell lymphoma. Oncotarget. 2016;7(27):41913–28.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Zhang H, Chen Z, Neelapu SS, Romaguera J, McCarty N. Hedgehog inhibitors selectively target cell migration and adhesion of mantle cell lymphoma in bone marrow microenvironment. Oncotarget. 2016;7(12):14350–65.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Lock R, Roy S, Kenific CM, Su JS, Salas E, Ronen SM, et al. Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol Biol Cell. 2011;22(2):165–78.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Guo JY, Chen HY, Mathew R, Fan J, Strohecker AM, Karsli-Uzunbas G, et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev. 2011;25(5):460–70.PubMedPubMedCentralGoogle Scholar
  104. 104.
    Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, et al. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017;129(13):1768–78.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Alinari L. Toward autophagy-targeted therapy in lymphoma. Blood. 2017;129(13):1740–2.PubMedGoogle Scholar
  106. 106.
    Blum KA, Lozanski G, Byrd JC. Adult Burkitt leukemia and lymphoma. Blood. 2004;104(10):3009–20.PubMedGoogle Scholar
  107. 107.
    Cai Q, Medeiros LJ, Xu X, Young KH. MYC-driven aggressive B-cell lymphomas: biology, entity, differential diagnosis and clinical management. Oncotarget. 2015;6(36):38591–616.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Nguyen L, Papenhausen P, Shao H. The role of c-MYC in B-cell lymphomas: diagnostic and molecular aspects. Genes (Basel). 2017;8(4):116.Google Scholar
  109. 109.
    Maclean KH, Dorsey FC, Cleveland JL, Kastan MB. Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis. J Clin Invest. 2008;118(1):79–88.PubMedGoogle Scholar
  110. 110.
    Dang CV. Antimalarial therapy prevents Myc-induced lymphoma. J Clin Invest. 2008;118(1):15–7.PubMedGoogle Scholar
  111. 111.
    Hart LS, Cunningham JT, Datta T, Dey S, Tameire F, Lehman SL, et al. ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth. J Clin Invest. 2012;122(12):4621–34.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Dey S, Tameire F, Koumenis C. PERK-ing up autophagy during MYC-induced tumorigenesis. Autophagy. 2013;9(4):612–4.PubMedPubMedCentralGoogle Scholar
  113. 113.
    Pujals A, Favre L, Pioche-Durieu C, Robert A, Meurice G, Le Gentil M, et al. Constitutive autophagy contributes to resistance to TP53-mediated apoptosis in Epstein–Barr virus-positive latency III B-cell lymphoproliferations. Autophagy. 2015;11(12):2275–87.PubMedPubMedCentralGoogle Scholar
  114. 114.
    De Leo A, Colavita F, Ciccosanti F, Fimia GM, Lieberman PM, Mattia E. Inhibition of autophagy in EBV-positive Burkitt’s lymphoma cells enhances EBV lytic genes expression and replication. Cell Death Dis. 2015;6:e1876.PubMedPubMedCentralGoogle Scholar
  115. 115.
    Rowe M, Kelly GL, Bell AI, Rickinson AB. Burkitt’s lymphoma: the Rosetta Stone deciphering Epstein–Barr virus biology. Semin Cancer Biol. 2009;19(6):377–88.PubMedPubMedCentralGoogle Scholar
  116. 116.
    Cloonan SM, Williams DC. The antidepressants maprotiline and fluoxetine induce Type II autophagic cell death in drug-resistant Burkitt’s lymphoma. Int J Cancer. 2011;128(7):1712–23.PubMedGoogle Scholar
  117. 117.
    Turzanski J, Daniels I, Haynes AP. Involvement of macroautophagy in the caspase-independent killing of Burkitt lymphoma cell lines by rituximab. Br J Haematol. 2009;145(1):137–40.PubMedGoogle Scholar
  118. 118.
    Gu L, Xie L, Zuo C, Ma Z, Zhang Y, Zhu Y, et al. Targeting mTOR/p70S6K/glycolysis signaling pathway restores glucocorticoid sensitivity to 4E-BP1 null Burkitt Lymphoma. BMC Cancer. 2015;15:529.PubMedPubMedCentralGoogle Scholar
  119. 119.
    Ni Z, Dai X, Wang B, Ding W, Cheng P, Xu L, et al. Natural Bcl-2 inhibitor (−)- gossypol induces protective autophagy via reactive oxygen species-high mobility group box 1 pathway in Burkitt lymphoma. Leuk Lymphoma. 2013;54(10):2263–8.PubMedGoogle Scholar
  120. 120.
    Re D, Thomas RK, Behringer K, Diehl V. From Hodgkin disease to Hodgkin lymphoma: biologic insights and therapeutic potential. Blood. 2005;105(12):4553–60.PubMedGoogle Scholar
  121. 121.
    Oehadian A, Koide N, Hassan F, Islam S, Mori I, Yoshida T, et al. Differential expression of autophagy in Hodgkin lymphoma cells treated with various anti-cancer drugs. Acta Med Indones. 2007;39(4):153–6.PubMedGoogle Scholar
  122. 122.
    Guidetti A, Carlo-Stella C, Locatelli SL, Malorni W, Pierdominici M, Barbati C, et al. Phase II study of sorafenib in patients with relapsed or refractory lymphoma. Br J Haematol. 2012;158(1):108–19.PubMedGoogle Scholar
  123. 123.
    Klein JM, Henke A, Sauer M, Bessler M, Reiners KS, Engert A, et al. The histone deacetylase inhibitor LBH589 (panobinostat) modulates the crosstalk of lymphocytes with Hodgkin lymphoma cell lines. PLoS One. 2013;8(11):e79502.PubMedPubMedCentralGoogle Scholar
  124. 124.
    Pierdominici M, Maselli A, Locatelli SL, Ciarlo L, Careddu G, Patrizio M, et al. Estrogen receptor beta ligation inhibits Hodgkin lymphoma growth by inducing autophagy. Oncotarget. 2017;8(5):8522–35.PubMedGoogle Scholar
  125. 125.
    Birkenmeier K, Moll K, Newrzela S, Hartmann S, Drose S, Hansmann ML. Basal autophagy is pivotal for Hodgkin and Reed–Sternberg cells’ survival and growth revealing a new strategy for Hodgkin lymphoma treatment. Oncotarget. 2016;7(29):46579–88.PubMedPubMedCentralGoogle Scholar
  126. 126.
    Yoshida GJ. Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: from pathophysiology to treatment. J Hematol Oncol. 2017;10(1):67.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Vogl DT, Stadtmauer EA, Tan KS, Heitjan DF, Davis LE, Pontiggia L, et al. Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy. 2014;10(8):1380–90.PubMedPubMedCentralGoogle Scholar
  128. 128.
    Amaravadi RK, Lippincott-Schwartz J, Yin XM, Weiss WA, Takebe N, Timmer W, et al. Principles and current strategies for targeting autophagy for cancer treatment. Clin Cancer Res. 2011;17(4):654–66.PubMedPubMedCentralGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  1. 1.Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeKunmingChina

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