Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

Experimental Cell Research

Volumn 324, Issue 1, 2014, Pages 1-12

  Orfali, Nina ^a,d   McKenna, Sharon L ^a   Cahill, Mary R ^b   Gudas, Lorraine J ^d   Mongan, Nigel P ^c,d  

^a UNIVERSITY COLLEGE CORK   (Ireland)

^b University College Cork and INFANT Centre   (Ireland)

^c UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^d WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

AML; APL; Arsenic trioxide; ATRA; Autophagy; Differentiation; Hematopoiesis; PML RAR ; Retinoid

Indexed keywords

CCAAT ENHANCER BINDING PROTEIN; RETINOID; RETINOL BINDING PROTEIN 4;

ACUTE GRANULOCYTIC LEUKEMIA; AUTOPHAGY; CATABOLISM; CELL DIFFERENTIATION; CELLS; CHROMATIN IMMUNOPRECIPITATION; CHROMOSOME TRANSLOCATION; CLINICAL TRIAL (TOPIC); CONFORMATIONAL TRANSITION; DISEASE FREE SURVIVAL; DOUBLE STRANDED DNA BREAK; EMBRYO DEVELOPMENT; EMBRYONIC STEM CELL; ERYTHROPOIESIS; FETUS LIVER; GENE EXPRESSION; GENE FUSION; GENE TRANSLOCATION; GENETIC TRANSCRIPTION; GENOTYPE; GRANULOCYTE; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL; HUMAN; INSULIN SENSITIVITY; INTESTINE ABSORPTION; INTRON; LEUKEMOGENESIS; MEMBRANE VESICLE; METABOLIC REGULATION; METABOLISM; NONHUMAN; PRIORITY JOURNAL; PROMYELOCYTIC LEUKEMIA; PROTEIN DEGRADATION; PROTEIN METABOLISM; REMISSION; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION;

AML; APL; ARSENIC TRIOXIDE; ATRA; AUTOPHAGY; DIFFERENTIATION; HEMATOPOIESIS; PML-RARΑ; RETINOID;

ANIMALS; AUTOPHAGY; CELL DIFFERENTIATION; HEMATOPOIESIS; HUMANS; LEUKEMIA, PROMYELOCYTIC, ACUTE; RECEPTORS, RETINOIC ACID; RETINOIDS; SIGNAL TRANSDUCTION;

EID: 84899482608     PISSN: 00144827     EISSN: 10902422     Source Type: Journal    
DOI: 10.1016/j.yexcr.2014.03.018     Document Type: Review

References (133)

1. Tang X.H., Gudas L.J. Retinoids, retinoic acid receptors, and cancer. Annu. Rev. Pathol. 2011, 6:345-364.
2. David K.A., Mongan N.P., Smith C., Gudas L.J., Nanus D.M. Phase I trial of ATRA-IV and depakote in patients with advanced solid tumor malignancies. Cancer Biol. Ther. 2010, 9:678-684.
3. Boorjian S.A., et al. Phase 1/2 clinical trial of interferon alpha2b and weekly liposome-encapsulated all-trans retinoic acid in patients with advanced renal cell carcinoma. J. Immunother. 1997, 30(655-662):2007.
4. Mongan N.P., Gudas L.J. Diverse actions of retinoid receptors in cancer prevention and treatment. Differentiation Research in Biological Diversity 2007, 75:853-870.
5. O'Byrne S.M., Blaner W.S. Retinol and retinyl esters: biochemistry and physiology: thematic review series: fat-soluble vitamins: vitamin A. J. Lipid Res. 2013, 54:1731-1743.
6. Yang Q., et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005, 436:356-362.
7. Berry D.C., Jin H., Majumdar A., Noy N. Signaling by vitamin A and retinol-binding protein regulates gene expression to inhibit insulin responses. Proc. Nat. Acad. Sci. U.S.A. 2011, 108:4340-4345.
8. Marwarha G., Berry D.C., Croniger C.M., Noy N. The retinol esterifying enzyme LRAT supports cell signaling by retinol-binding protein and its receptor STRA6. FASEB J.: Official Publication of the Federation of American Societies for Experimental Biology 2014, 28:26-34.
9. Muenzner M., et al. Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor alpha activity. Mol. Cell. Biol. 2013, 33:4068-4082.
10. Berry D.C., et al. The STRA6 receptor is essential for retinol-binding protein-induced insulin resistance but not for maintaining vitamin A homeostasis in tissues other than the eye. J. Biol. Chem. 2013, 288:24528-24539.
11. Kawaguchi R., et al. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science 2007, 315:820-825.
12. Amengual J., Golczak M., Palczewski K., von Lintig J. Lecithin: retinol acyltransferase is critical for cellular uptake of vitamin A from serum retinol-binding protein. J. Biol. Chem. 2012, 287:24216-24227.
13. Germain P., et al. International Union of Pharmacology. LXIII. Retinoid X receptors. Pharmacol. Rev. 2006, 58:760-772.
14. Germain P., et al. International Union of Pharmacology. LX. Retinoic acid receptors. Pharmacol. Rev. 2006, 58:712-725.
15. Gillespie R., Gudas L. RAR isotype specificity in F9 teratocarcinoma stem cells results from the differential recruitment of coregulators to retinoic acid response elements. J. Biol. Chem. 2007, 282:33421-33434.
16. Giguere V., Ong E.S., Segui P., Evans R.M. Identification of a receptor for the morphogen retinoic acid. Nature 1987, 330:624-629.
17. Brand N., et al. Identification of a second human retinoic acid receptor. Nature 1988, 332:850-853.
18. Krust A., Kastner P., Petkovich M., Zelent A., Chambon P. A third human retinoic acid receptor, hRAR-gamma. Proc. Nat. Acad. Sci. U.S.A. 1989, 86:5310-5314.
19. Levin A.A., et al. 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. Nature 1992, 355:359-361.
20. Heyman R.A., et al. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 1992, 68:397-406.
21. Lee S., Privalsky M.L. Heterodimers of retinoic acid receptors and thyroid hormone receptors display unique combinatorial regulatory properties. Mol. Endocrinol. 2005, 19:863-878.
22. Michalik L., et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol. Rev. 2006, 58:726-741.
23. Germain P., Iyer J., Zechel C., Gronemeyer H. Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature 2002, 415:187-192.
24. Sohn Y.C., et al. Dynamic inhibition of nuclear receptor activation by corepressor binding. Mol. Endocrinol. 2003, 17:366-372.
25. Perissi V., et al. Molecular determinants of nuclear receptor-corepressor interaction. Genes Dev. 1999, 13:3198-3208.
26. Chen J.D., Evans R.M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 1995, 377:454-457.
27. Westin S., et al. Interactions controlling the assembly of nuclear-receptor heterodimers and co-activators. Nature 1998, 395:199-202.
28. Nagy L., et al. Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell 1997, 89:373-380.
29. Rochel N., et al. Common architecture of nuclear receptor heterodimers on DNA direct repeat elements with different spacings. Nat. Struct. Mol. Biol. 2011, 18:564-570.
30. Yao T.P., Ku G., Zhou N., Scully R., Livingston D.M. The nuclear hormone receptor coactivator SRC-1 is a specific target of p300. Proc. Nat. Acad. Sci. U.S.A. 1996, 93:10626-10631.
31. Shao W., et al. Ligand-inducible interaction of the DRIP/TRAP coactivator complex with retinoid receptors in retinoic acid-sensitive and -resistant acute promyelocytic leukemia cells. Blood 2000, 96:2233-2239.
32. Epping M.T., et al. The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell 2005, 122:835-847.
33. White K.A., et al. Negative feedback at the level of nuclear receptor coregulation. Self-limitation of retinoid signaling by RIP140. J. Biol. Chem. 2003, 278:43889-43892.
34. Wei L.N., Farooqui M., Hu X. Ligand-dependent formation of retinoid receptors, receptor-interacting protein 140 (RIP140), and histone deacetylase complex is mediated by a novel receptor-interacting motif of RIP140. J. Biol. Chem. 2001, 276:16107-16112.
35. Laursen K.B., et al. Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene. Nucleic Acids Res. 2013, 41:6430-6443.
36. Gudas L.J. Retinoids and vertebrate development. J. Biol. Chem. 1994, 269:15399-15402.
37. Laursen K.B., Wong P.M., Gudas L.J. Epigenetic regulation by RARalpha maintains ligand-independent transcriptional activity. Nucleic Acids Res. 2012, 40:102-115.
38. Kashyap V., Gudas L.J. Epigenetic regulatory mechanisms distinguish retinoic acid-mediated transcriptional responses in stem cells and fibroblasts. J. Biol. Chem. 2010, 285:14534-14548.
39. Kashyap V., et al. Epigenomic reorganization of the clustered Hox genes in embryonic stem cells induced by retinoic acid. J. Biol. Chem. 2011, 286:3250-3260.
40. Seita J., Weissman I.L. Hematopoietic stem cell: self-renewal versus differentiation. Wiley Interdiscip. Rev. Syst. Biol. Med. 2010, 2:640-653.
41. Guan J.L., et al. Autophagy in stem cells. Autophagy 2013, 9:830-849.
42. Oren T., Sher J.A., Evans T. Hematopoiesis and retinoids: development and disease. Leuk. Lymphoma 2003, 44:1881-1891.
43. Purton L.E., Bernstein I.D., Collins S.J. All-trans retinoic acid enhances the long-term repopulating activity of cultured hematopoietic stem cells. Blood 2000, 95:470-477.
44. Purton L.E., et al. RARgamma is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation. J. Exp. Med. 2006, 203:1283-1293.
45. Ghatpande S., Ghatpande A., Sher J., Zile M.H., Evans T. Retinoid signaling regulates primitive (yolk sac) hematopoiesis. Blood 2002, 99:2379-2386.
46. Ross A.C. Vitamin A and retinoic acid in T cell-related immunity. Am. J. Clin. Nutr. 2012, 96:1166S-1172S.
47. Mucida D., et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007, 317:256-260.
48. Jones R.J., et al. Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. Blood 1996, 88:487-491.
49. Park D.J., et al. CCAAT/enhancer binding protein epsilon is a potential retinoid target gene in acute promyelocytic leukemia treatment. J. Clin. Invest. 1999, 103:1399-1408.
50. Mueller B.U., et al. ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression. Blood 2006, 107:3330-3338.
51. Kastner P., et al. Positive and negative regulation of granulopoiesis by endogenous RARalpha. Blood 2001, 97:1314-1320.
52. Collins S.J. The role of retinoids and retinoic acid receptors in normal hematopoiesis. Leukemia 2002, 16:1896-1905.
53. Hasserjian R.P. Acute myeloid leukemia: advances in diagnosis and classification. Int. J. Lab. Hematol. 2013, 35:358-366.
54. Kuhnl A., Grimwade D. Molecular markers in acute myeloid leukaemia. Int. J. Hematol. 2012, 96:153-163.
55. Estey E.H. Acute myeloid leukemia: 2013 update on risk-stratification and management. Am. J. Hematol. 2013, 88:318-327.
56. Nowak D., Stewart D., Koeffler H.P. Differentiation therapy of leukemia: 3 decades of development. Blood 2009, 113:3655-3665.
57. de The H., Chomienne C., Lanotte M., Degos L., Dejean A. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature 1990, 347:558-561.
58. Borrow J., Goddard A.D., Sheer D., Solomon E. Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17. Science 1990, 249:1577-1580.
59. Choudhry A., DeLoughery T.G. Bleeding and thrombosis in acute promyelocytic leukemia. Am. J. Hematol. 2012, 87:596-603.
60. Yamamoto Y., et al. BCOR as a novel fusion partner of retinoic acid receptor alpha in a t(X;17)(p11;q12) variant of acute promyelocytic leukemia. Blood 2010, 116:4274-4283.
61. Won D., et al. OBFC2A/RARA: a novel fusion gene in variant acute promyelocytic leukemia. Blood 2013, 121:1432-1435.
62. Chen Z., et al. Fusion between a novel Kruppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J. 1993, 12:1161-1167.
63. Redner R.L., Rush E.A., Faas S., Rudert W.A., Corey S.J. The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. Blood 1996, 87:882-886.
64. Wells R.A., Catzavelos C., Kamel-Reid S. Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia. Nat. Genet. 1997, 17:109-113.
65. Arnould C., et al. The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor alpha in acute promyelocytic-like leukaemia. Hum. Mol. Gen. 1999, 8:1741-1749.
66. Catalano A., et al. The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia. Blood 2007, 110:4073-4076.
67. Kondo T., et al. The seventh pathogenic fusion gene FIP1L1-RARA was isolated from a t(4;17)-positive acute promyelocytic leukemia. Haematologica 2008, 93:1414-1416.
68. Tomlins S.A., et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005, 310:644-648.
69. Bastus N.C., et al. Androgen-induced TMPRSS2:ERG fusion in nonmalignant prostate epithelial cells. Cancer Res. 2010, 70:9544-9548.
70. Mani R.S., et al. Induced chromosomal proximity and gene fusions in prostate cancer. Science 2009, 326:1230.
71. Lin C., et al. Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer. Cell 2009, 139:1069-1083.
72. Martens J.H., et al. PML-RARalpha/RXR Alters the epigenetic landscape in acute promyelocytic leukemia. Cancer Cell 2010, 17:173-185.
73. Di Croce L., et al. Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 2002, 295:1079-1082.
74. Zhou J., et al. Dimerization-induced corepressor binding and relaxed DNA-binding specificity are critical for PML/RARA-induced immortalization. Proc. Nat. Acad. Sci. U.S.A. 2006, 103:9238-9243.
75. Lengfelder E., Hofmann W.K., Nolte F. Management of elderly patients with acute promyelocytic leukemia: progress and problems. Ann. Hematol. 2013, 92:1181-1188.
76. Grignani F., et al. Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature 1998, 391:815-818.
77. Collins S.J. Retinoic acid receptors, hematopoiesis and leukemogenesis. Curr. Opin. Hematol. 2008, 15:346-351.
78. Arrowsmith C.H., Bountra C., Fish P.V., Lee K., Schapira M. Epigenetic protein families: a new frontier for drug discovery. Nat. Rev. Drug Discovery 2012, 11:384-400.
79. Breitman T.R., Selonick S.E., Collins S.J. Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc. Nat. Acad. Sci. U.S.A. 1980, 77:2936-2940.
80. Breitman T.R., Collins S.J., Keene B.R. Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid. Blood 1981, 57:1000-1004.
81. Huang M.E., et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988, 72:567-572.
82. Tallman M.S., et al. All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol. Blood 2002, 100:4298-4302.
83. Wang Z.Y., Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 2008, 111:2505-2515.
84. Schlenk R.F., et al. Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B. Haematologica 2009, 94:54-60.
85. Estey E.H., et al. Randomized phase II study of fludarabine+cytosine arabinoside+idarubicin +/- all-trans retinoic acid +/- granulocyte colony-stimulating factor in poor prognosis newly diagnosed acute myeloid leukemia and myelodysplastic syndrome. Blood 1999, 93:2478-2484.
86. Nazha A., et al. The addition of all-trans retinoic acid to chemotherapy may not improve the outcome of patient with NPM1 mutated acute myeloid leukemia. Front. Oncol. 2013, 3:218.
87. Burnett A.K., et al. The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA. Blood 2010, 115:948-956.
88. Tomita A., Kiyoi H., Naoe T. Mechanisms of action and resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (As2O 3) in acute promyelocytic leukemia. Int. J. Hematol. 2013, 97:717-725.
89. Nervi C., et al. Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein. Blood 1998, 92:2244-2251.
90. Nasr R., et al. Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation. Nat. Med. 2008, 14:1333-1342.
91. vom Baur E., et al. Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1. EMBO J. 1996, 15:110-124.
92. Yoshida H., et al. Accelerated degradation of PML-retinoic acid receptor alpha (PML-RARA) oncoprotein by all-trans-retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway. Cancer Res. 1996, 56:2945-2948.
93. Ablain J., et al. Uncoupling RARA transcriptional activation and degradation clarifies the bases for APL response to therapies. J. Exp. Med. 2013, 210:647-653.
94. Dos Santos G.A., Kats L., Pandolfi P.P. Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia. J. Exp. Med. 2013, 210:2793-2802.
95. Fung T.K., So E.C. Overcoming treatment resistance in acute promyelocytic leukemia and beyond. Oncotarget 2013, 4:1128-1129.
96. Muindi J., et al. Continuous treatment with all-trans retinoic acid causes a progressive reduction in plasma drug concentrations: implications for relapse and retinoid "resistance" in patients with acute promyelocytic leukemia. Blood 1992, 79:299-303.
97. He L.Z., et al. Distinct interactions of PML-RARalpha and PLZF-RARalpha with co-repressors determine differential responses to RA in APL. Nat. Genet. 1998, 18:126-135.
98. Chen G.Q., et al. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood 1996, 88:1052-1061.
99. Ghavamzadeh A., et al. Phase II study of single-agent arsenic trioxide for the front-line therapy of acute promyelocytic leukemia. J. Clin. Oncol.: Official Journal of the American Society of Clinical Oncology 2011, 29:2753-2757.
100. Estey E., et al. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood 2006, 107:3469-3473.
101. Lo-Coco F., et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N. Engl. J. Med. 2013, 369:111-121.
102. Chen G.Q., et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood 1997, 89:3345-3353.
103. Goussetis D.J., et al. Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide. J. Biol. Chem. 2010, 285:29989-29997.
104. Chen Y., Klionsky D.J. The regulation of autophagy-unanswered questions. J. Cell Sci. 2011, 124:161-170.
105. Choi A.M., Ryter S.W., Levine B. Autophagy in human health and disease. N. Engl. J. Med. 2013, 368:1845-1846.
106. Nakatogawa H., Suzuki K., Kamada Y., Ohsumi Y. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat. Rev. Mol. Cell Biol. 2009, 10:458-467.
107. He C., Klionsky D.J. Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet. 2009, 43:67-93.
108. Yang Z., Klionsky D.J. Mammalian autophagy: core molecular machinery and signaling regulation. Curr. Opin. Cell Biol. 2010, 22:124-131.
109. Kroemer G., Marino G., Levine B. Autophagy and the integrated stress response. Mol. Cell 2010, 40:280-293.
110. Rubinsztein D.C., Marino G., Kroemer G. Autophagy and aging. Cell 2011, 146:682-695.
111. Fleming A., Noda T., Yoshimori T., Rubinsztein D.C. Chemical modulators of autophagy as biological probes and potential therapeutics. Nat. Chem. Biol. 2011, 7:9-17.
112. Palmieri M., et al. Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. Hum. Mol. Gen. 2011, 20:3852-3866.
113. Zhang H., et al. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J. Biol. Chem. 2008, 283:10892-10903.
114. Polager S., Ofir M., Ginsberg D. E2F1 regulates autophagy and the transcription of autophagy genes. Oncogene 2008, 27:4860-4864.
115. Tsukamoto S., et al. Autophagy is essential for preimplantation development of mouse embryos. Science 2008, 321:117-120.
116. Tra T., et al. Autophagy in human embryonic stem cells. PLoS One 2011, 6:e27485.
117. Kang Y.A., et al. Autophagy driven by a master regulator of hematopoiesis. Mol. Cell. Biol. 2012, 32:226-239.
118. Yousefi S., Simon H.U. Autophagy in cells of the blood. Biochim. Biophys. Acta 1793, 1461-1464:2009.
119. Conway K.L., et al. ATG5 regulates plasma cell differentiation. Autophagy 2013, 9.
120. Zhang Y., Morgan M.J., Chen K., Choksi S., Liu Z.G. Induction of autophagy is essential for monocyte-macrophage differentiation. Blood 2012, 119:2895-2905.
121. Yue Z., Jin S., Yang C., Levine A.J., Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Nat. Acad. Sci. U.S.A. 2003, 100:15077-15082.
122. Laplante M., Sabatini D.M. mTOR signaling in growth control and disease. Cell 2012, 149:274-293.
123. Liu F., et al. FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells. Blood 2010, 116:4806-4814.
124. Mortensen M., et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J. Exp. Med. 2011, 208:455-467.
125. Su M., Mei Y., Sinha S. Role of the crosstalk between autophagy and apoptosis in cancer. J. Oncol. 2013, 2013:102735.
126. Trocoli A., et al. ATRA-induced upregulation of Beclin 1 prolongs the life span of differentiated acute promyelocytic leukemia cells. Autophagy 2011, 7:1108-1114.
127. Wang Z., et al. Autophagy regulates myeloid cell differentiation by p62/SQSTM1-mediated degradation of PML-RARalpha oncoprotein. Autophagy 2011, 7:401-411.
128. Isakson P., Bjoras M., Boe S.O., Simonsen A. Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein. Blood 2010, 116:2324-2331.
129. Brigger D., Torbett B.E., Chen J., Fey M.F., Tschan M.P. Inhibition of GATE-16 attenuates ATRA-induced neutrophil differentiation of APL cells and interferes with autophagosome formation. Biochem. Biophys. Res. Commun. 2013, 438:283-288.
130. Fullgrabe J., Klionsky D.J., Joseph B. The return of the nucleus: transcriptional and epigenetic control of autophagy. Nat. Rev. Mol. Cell Biol. 2014, 15:65-74.
131. Rajawat Y., Hilioti Z., Bossis I. Retinoic acid induces autophagosome maturation through redistribution of the cation-independent mannose-6-phosphate receptor. Antioxidants Redox Signaling 2011, 14:2165-2177.
132. Elzinga B.M., et al. Induction of autophagy by Imatinib sequesters Bcr-Abl in autophagosomes and down-regulates Bcr-Abl protein. Am. J. Hematol. 2013, 88:455-462.
133. Torgersen M.L., Engedal N., Boe S.O., Hokland P., Simonsen A. Targeting autophagy potentiates the apoptotic effect of histone deacetylase inhibitors in t(8;21) AML cells. Blood 2013, 122:2467-2476.