Differentiation therapy of acute myeloid leukemia: Past, present and future

Current Opinion in Hematology

Volumn 16, Issue 2, 2009, Pages 84-91

  Petrie, Kevin ^a   Zelent, Arthur ^a   Waxman, Samuel ^b  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Acute myeloid leukemia; All trans retinoic acid; Differentiation therapy; Retinoic acid receptor

Indexed keywords

2 (2,4 DICHLOROPHENYL) 3 (1 METHYL 3 INDOLYL)MALEIMIDE; 5 AZA 2' DEOXYCYTIDINE; ARSENIC TRIOXIDE; AZACITIDINE; DITERPENOID; DNA METHYLTRANSFERASE INHIBITOR; ERIOCALYXIN B; HISTONE DEACETYLASE INHIBITOR; N (2 AMINOPHENYL) 4 [4 (3 PYRIDINYL) 2 PYRIMIDINYLAMINOMETHYL]BENZAMIDE; ORIDONIN; RETINOIC ACID; RETINOIC ACID RECEPTOR ALPHA; TANESPIMYCIN; TUBACIN; UNCLASSIFIED DRUG; VALPROIC ACID; VORINOSTAT;

ACUTE GRANULOCYTIC LEUKEMIA; CELL PROLIFERATION; CELL SURVIVAL; CHEMOTHERAPY; CLINICAL TRIAL; CUTANEOUS T CELL LYMPHOMA; DNA METHYLATION; DRUG EFFICACY; EPIGENETICS; GENE CONTROL; GENE EXPRESSION; GENE MUTATION; GENOMICS; HIGH THROUGHPUT SCREENING; HUMAN; KARYOTYPE; LEUKOENCEPHALOPATHY; MYELODYSPLASTIC SYNDROME; NONHUMAN; PRIORITY JOURNAL; PROMYELOCYTIC LEUKEMIA; REVIEW; SIGNAL TRANSDUCTION;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; ARSENICALS; HUMANS; LEUKEMIA, MYELOID, ACUTE; OXIDES; RECEPTORS, RETINOIC ACID; SENSITIVITY AND SPECIFICITY; TRETINOIN;

EID: 62249169964     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/MOH.0b013e3283257aee     Document Type: Review

References (73)

1. Hillestad LK. Acute promyelocytic leukemia. Acta Med Scand 1957; 159: 189-194.
2. Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 2008; 111:2505-2515. This is a comprehensive review charting the history of differentiation therapy in APL.
3. Fibach E, Hayashi M, Sachs L. Control of normal differentiation of myeloid leukemic cells to macrophages and granulocytes. Proc Natl Acad Sci USA 1973; 70:343-346.
4. Sachs L. The differentiation of myeloid leukaemia cells: new possibilities for therapy. Br J Haematol 1978; 40:509-517.
5. Breitman TR, Selonick SE, Collins SJ. Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci USA 1980; 77:2936-2940.
6. Breitman TR, Collins SJ, Keene BR. Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid. Blood 1981; 57:1000-1004.
7. Waxman S, Scher W, Scher BM. Basic principles for utilizing combination differentiation agents. In: Niebergs HE, editor. Sixth International Symposium for the Detection and Prevention of Cancer. New York: Vienna: Alan Liss Inc; 1984.
8. Huang ME, Ye YC, Chen SR, et al. All-trans retinoic acid with or without low dose cytosine arabinoside in acute promyelocytic leukaemia. Report of 6 cases. Chin Med J (Engl) 1987; 100:949-953.
9. Huang ME, Ye YC, Chen SR, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988; 72:567-572.
10. Chen Z, Brand NJ, Chen A, 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.
11. Licht JD, Chomienne C, Goy A, et al. Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation (11;17). Blood 1995; 85:1083-1094.
12. Zhu J, Chen Z, Lallemand-Breitenbach V, et al. How acute promyelocytic leukaemia revived arsenic. Nat Rev Cancer 2002; 2:705-713.
13. Schlenk RF, Frohling S, Hartmann F, et al. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia 2004; 18:1798-1803.
14. Di Febo A, Laurenti L, Falcucci P, et al. All-trans retinoic acid in association with low dose cytosine arabinoside in the treatment of acute myeloid leukemia in elderly patients. Am J Ther 2007; 14:351-355.
15. Bug G, Ritter M, Wassmann B, et al. Clinical trial of valproicacid and all-trans retinoic acid in patients with poor-risk acute myeloid leukemia. Cancer 2005; 104:2717-2725.
16. Craddock C, Bradbury C, Narayanan S, et al. Predictors of clinical response in patients with high risk acute myeloid leukemia receiving treatment with the histone deacetylase inhibitor sodium valproate. ASH Annual Meeting Abstracts 2005; 106:2791.
17. Kuendgen A, Schmid M, Schlenk R, et al. The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia. Cancer 2006; 106:112-119.
18. Soriano AO, Yang H, Faderl S, et al. Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood 2007; 110:2302-2308. This clinical study indicates that combining ATRA with decitabine and valproic acid can be beneficial the treatment of non-APL AML.
19. Zelent A, Petrie K, Boix-Chornet M, et al. Derepression in the desert: the third workshop on clinical translation of epigenetics in cancer therapeutics. Cancer Res 2008; 68:4967-4970.
20. Glasow A, Prodromou N, Xu K, et al. Retinoids and myelomonocytic growth factors cooperatively activate RARA and induce human myeloid leukemia cell differentiation via MAP kinase pathways. Blood 2005; 105:341-349.
21. Zhu J, Heyworth CM, Glasow A, et al. Lineage restriction of the RARalpha gene expression in myeloid differentiation. Blood 2001; 98:2563-2567.
22. Altucci L, Gronemeyer H. The promise of retinoids to fight against cancer. Nat Rev Cancer 2001; 1:181-193.
23. Gilliland DG, Tallman MS. Focus on acute leukemias. Cancer Cell 2002; 1:417-420.
24. Zheng X, Seshire A, Ruster B, et al. Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RARalpha-positive leukemic stem cells. Haematologica 2007; 92:323-331. This study shows that arsenic trioxide but not ATRA can overcome the aberrant stem cell capacity of PML/RARα-positive leukemic stem cells.
25. Tatham MH, Geoffroy MC, Shen L, et al. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol 2008; 10:538-546. Along with [26**], this study identify PML as an in-vivo target of the RING finger ubiquitin E3 ligase RNF4, which specifically binds poiysumoylated PML via four tandem SUMO interaction motifs and is essential for the arsenic-induced catabolism of both PML and PML-RARα.
26. Lallemand-Breitenbach V, Jeanne M, Benhenda S, et al. Arsenic degrades PML or PML-RARalpha through a SUMO-triggered RNF4/ubiquitin-mediated pathway. Nat Cell Biol 2008; 10:547-555. Along with [25**], this study identify PML as an in-vivo target of the RING finger ubiquitin E3 ligase RNF4, which specifically binds poiysumoylated PML via four tandem SUMO interaction motifs and is essential for the arsenic-induced catabolism of both PML and PML-RARα.
27. Petrie K, Zelent A. Marked for death. Nat Cell Biol 2008; 10:507-509.
28. Plass C, Oakes C, Slum W, et al. Epigenetics in acute myeloid leukemia. Semin Oncol 2008; 35:378-387.
29. Fazi F, Zardo G, Gelmetti V, et al. Heterochromatic gene repression of the retinoic acid pathway in acute myeloid leukemia. Blood 2007; 109:4432-4440. This study suggests that the retinoic acid signaling pathway is blocked by AML1/ETO. This is because the fusion oncoprotein recruits negatively acting epigenetic factors to RARα target gene promoters and offers an explanation as to why AML1/ETO-associated AML does not respond to ATRA.
30. Glasow A, Barrett A, Petrie K, et al. DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia. Blood 2008; 111:2374-2377. This study demonstrates that loss of RARA expression in primary AML cells is not associated with promoter hypermethylation, but rather diminished levels of histone H3 acetylation and lysine 4 methylation. These results highlight for the first time existence of DNA methylation independent and histone code driven gene-silencing mechanisms in cancer pathogenesis.
31. Kondo Y, Shen L, Cheng AS, et al. Gene silencing in cancer by histone H3 lysine 27 trimethylation independant of promoter DNA methylation. Nat Genet 2008; 40:741-750. This study demonstrates that H3K27 trimethylation is associated with DNA methylation-independent gene silencing in prostate cancer.
32. Jepsen K, Solum D, Zhou T, et al. SMRT-mediated repression of an H3K27 demethylase in progression from neural stem cell to neuron. Nature 2007; 450:415-419. JMJD3 functions as a trimethyl H3K27 demethylase and is ATRA-regulated during neural cell differentiation. This indicates that H3K27 methylation plays a role in the myeloid differentiation and possibly AML.
33. Koken MH, Daniel MT, Gianni M, et al. Retinoic acid, but not arsenic trioxide, degrades the PLZF/RARalpha fusion protein, without inducing terminal differentiation or apoptosis, in a RA-therapy resistant t(11;17)(q23;q21) APL patient. Oncogene 1999; 18:1113-1118.
34. Guidez F, Ivins S, Zhu J, et al. Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia. Blood 1998; 91:2634-2642.
35. He LZ, Guidez F, Tribioli C, 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.
36. Guidez F, Parks S, Wong H, et al. RARalpha-PLZF overcomes PLZF-mediated repression of CRABPI, contributing to retinoid resistance in t(11;17) acute promyelocytic leukemia. Proc Natl Acad Sci U S A 2007; 104:18694-18699.
37. Glass CK, Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 2000; 14:121-141.
38. van Wely KH, Meester-Smoor MA, Janssen MJ, et al. The MN1-TEL myeloid leukemia-associated fusion protein has a dominant-negative effect on RAR-RXR-mediated transcription. Oncogene 2007; 26:5733-5740. The MN1-TEL myeloid leukemia-associated fusion protein inhibits RAR-RXR-mediated transcription in response to ATRA signaling.
39. Carella C, Bonten J, Sirma S, et al. MN1 overexpression is an important step in the development of inv(16) AML Leukemia 2007; 21:1679-1690.
40. Heuser M, Beutel G, Krauter J, et al. High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood 2006; 108:3898-3905.
41. Meester-Smoor MA, Janssen MJ, Grosveld GC, et al. MN1 affects expression of genes involved in hematopoiesis and can enhance as well as inhibit RAR/RXR induced gene expression. Carcinogenesis 2008; 29:2025-2034. MN1 can interfere with the ATRA pathway by blocking expression of ATRA target genes. MN1 is overexpressed in some AML subtypes and this may contribute to the lack of ATRA responsiveness in these cases.
42. Zelent A, Petrie K, Lotan R, et al. Clinical translation of epigenetics in cancer: eN-CORe-a report on the second workshop. Mol Cancer Ther 2005; 4: 1810-1819.
43. Somoza JR, Skene RJ, Katz BA, et al. Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure (Camb) 2004; 12:1325-1334.
44. Bug G, Schwarz K, Schoch C, et al. Effect of histone deacetylase inhibitor valproic acid on progenitor cells of acute myeloid leukemia. Haematologica 2007; 92:542-545. This study highlights a potential problem with use of valproic acid and possibly other nonselective histone deacetylase inhibitors in the treatment AML as it causes proliferation of leukemic progenitor cells.
45. Bali P, Pranpat M, Bradner J, et al. Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem 2005; 280:26729-26734.
46. Rao R, Fiskus W, Yang Y, et al. HDAC6 inhibition enhances 17-AAG-mediated abrogation of hsp90 chaperone function in human leukemia cells. Blood 2008; 112:1886-1893.
47. Seekers T, Burkhardt C, Wieland H, et al. Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group. Int J Cancer 2007; 121:1138-1148.
48. Fournel M, Bonfils C, Hou Y, et al. MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. Mol Cancer Ther 2008; 7:759-768.
49. Rice KL, Hormaeche I, Licht JD. Epigenetic regulation of normal and malignant hematopoiesis. Oncogene 2007; 26:6697-6714.
50. Tan J, Yang X, Zhuang L, et al. Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev 2007; 21:1050-1063.
51. Kubicek S, O'Sullivan RJ, August EM, et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 2007; 25:473-481.
52. Huang Y, Greene E, Murray Stewart T, et al. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes. Proc Natl Acad Sci U S A 2007; 104:8023-8028.
53. Lee MG, Wynder C, Schmidt DM, et al. Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chem Biol 2006; 13:563-567.
54. Metzger E, Wissmann M, Yin N, et al. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 2005; 437:436-439.
55. Scholl C, Gilliland DG, Frohling S. Deregulation of signaling pathways in acute myeloid leukemia. Semin Oncol 2008; 35:336-345.
56. Licht JD, Zelent A. Retinoid and growth factor receptor signaling in APL. Blood 2005; 105:1381-1382.
57. Purton LE, Bernstein ID, Collins SJ. All-trans retinoic acid enhances the long-term repopulating activity of cultured hematopoietic stem cells. Blood 2000; 95:470-477.
58. Purton LE, Dworkin S, Olsen GH, et al. RARgamma is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation. J Exp Med 2006; 203:1283-1293.
59. Hattori H, Zhang X, Jia Y, et al. RNAi screen identifies UBE2D3 as a mediator of all-trans retinoic acid-induced cell growth arrest in human acute promyelocytic NB4 cells. Blood 2007; 110:640-650. This is the first example of the use of functional genomics to screen for factors that influence ATRA-induced differentiation.
60. Wald DN, Vermaat HM, Zang S, et al. Identification of 6-benzylthioinosine as a myeloid leukemia differentiation-inducing compound. Cancer Res 2008; 68:4369-4376. This study carried out a small molecule differentiation screen with over 6000 compounds and identified 6-benzylthioinosine as an agent that can induce differentiation in AML.
61. Wang Z, Smith KS, Murphy M, et al. Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy Nature 2008; 455:1205-1209.
62. Wang L, Zhao WL, Van JS, et al. Eriocalyxin B induces apoptosis of t(8;21 ) leukemia cells through NF-kappaB and MARK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner. Cell Death Differ 2007; 14:306-317.
63. Zhou GB, Kang H, Wang L, et al. Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8;21 ) leukemia in vitro and in vivo. Blood 2007; 109:3441-3450.
64. Shackelford D, Kenific C, Blusztajn A, et al. Targeted degradation of the AML1/MDS1/EVI1 oncoprotein by arsenic trioxide. Cancer Res 2006; 66:11360-11369.
65. Ito K, Bernardi R, Morotti A, et al. PML targeting eradicates quiescent leukaemia-initiating cells. Nature 2008; 453:1072-1078.
66. Dilda PJ, Hogg PJ. Arsenical-based cancer drugs. Cancer Treat Rev 2007; 33:542-564.
67. Racanicchi S, Maccherani C, Liberatore C, et al. Targeting fusion protein/corepressor contact restores differentiation response in leukemia cells. Embo J 2005; 24:1232-1242.
68. Jing Y, Hellinger N, Xia L, et al. Benzocdithiophenes induce differentiation and apoptosis in human leukemia cells. Cancer Res 2005; 65:7847-7855.
69. Xu K, Guidez F, Glasow A, et al. Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor alpha and enhancing changes in all-trans-retinoic acid-regulated gene expression. Cancer Res 2005; 65:7856-7865.
70. Gorczynski MJ, Grembecka J, Zhou Y, et al. Allosteric inhibition of the protein-protein interaction between the leukemia-associated proteins Runx1 and CBFbeta. Chem Biol 2007; 14:1186-1197.
71. Douvas MG, Roudaiya L, Grembecka J, et al. Development of allosteric inhibitors of the interaction of AML1 and CBF for the treatment of leukemia. ASH Annual Meeting Abstracts 2007; 110:653.
72. Vassilev LT, Vu BT, Graves B, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004; 303:844-848.
73. Secchiero P, Zerbinati C, Melloni E, et al. The MDM-2 antagonist nutlin-3 promotes the maturation of acute myeloid leukemic blasts. Neoplasia 2007; 9:853-861.