A critical review of the molecular pathophysiology of lenalidomide sensitivity in 5q - Myelodysplastic syndromes

Leukemia and Lymphoma

Volumn 53, Issue 5, 2012, Pages 779-788

  Voutsadakis, Ioannis A ^a   Cairoli, Anne ^a  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

Author keywords

5q syndrome; cell adhesion; haploinsufficiency; lenalidomide; Myelodysplastic syndromes; NF B

Indexed keywords

A20 BINDING INHIBITOR OF NF KAPPA B; ALPHA CATENIN; BORTEZOMIB; CALPHOBINDIN II; CASEIN KINASE IALPHA; CD74 ANTIGEN; DEFERASIROX; EARLY GROWTH RESPONSE FACTOR 1; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; GAMMA INTERFERON; GLUTATHIONE PEROXIDASE 3; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR RECEPTOR; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; HEPARAN SULFATE; I KAPPA B KINASE GAMMA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1BETA; INTERLEUKIN 6; LENALIDOMIDE; OSTEONECTIN; PROTEIN; PROTEIN TYROSINE PHOSPHATASE; STEROID; SUPPRESSOR OF CYTOKINE SIGNALING 1; TRANSCRIPTION FACTOR FOXP3; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULAR CELL ADHESION MOLECULE 1; VASCULOTROPIN RECEPTOR;

5Q- SYNDROME; CELL CYCLE; CHROMOSOME 5Q; CHROMOSOME DELETION; CYTOKINE PRODUCTION; CYTOSKELETON; CYTOTOXICITY; DOWN REGULATION; DRUG ACTIVITY; DRUG EFFECT; DRUG SENSITIVITY; GENE MUTATION; GENETIC CODE; GENETIC RISK; HAPLOINSUFFICIENCY; HETEROZYGOSITY; HISTOCOMPATIBILITY; HUMAN; IMMUNOMODULATION; LYMPHOCYTE FUNCTION; LYMPHOCYTE PROLIFERATION; MACROCYTIC ANEMIA; MEGAKARYOCYTE; MOLECULAR PATHOLOGY; MULTIPLE MYELOMA; MYELOMA CELL; NATURAL KILLER T CELL; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROGNOSIS; PROTEIN DEPHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; THROMBOCYTE COUNT; THROMBOCYTOSIS; TREATMENT RESPONSE; UPREGULATION;

ANTINEOPLASTIC AGENTS; CHROMOSOME DELETION; CHROMOSOMES, HUMAN, PAIR 5; HAPLOINSUFFICIENCY; HUMANS; MYELODYSPLASTIC SYNDROMES; THALIDOMIDE;

EID: 84859995673     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.3109/10428194.2011.623255     Document Type: Review

References (107)

1. Ebert BL. Deletion 5q in myelodysplastic syndrome: A paradigm for the study of hemizygous deletions in cancer. Leukemia 2009;23:1252-1256.
2. Boultwood J, Fidler C, Strickson AJ, et al. Narrowing and genomic annotation of the commonly deleted region of the 5q- syndrome. Blood 2002;99:4638-4641. (Pubitemid 34627240)
3. Barlow JL, Drynan LF, Trim NL, et al. New insights into 5qsyndrome as a ribosomopathy. Cell Cycle 2010;9:4286-4293.
4. Giagounidis AAN, Germing U, Haase S, et al. Clinical, morphological, cytogenetic, and prognostic features of patients wiThmyelodysplastic syndromes and del(5q) including band q31. Leukemia 2004;18:113-119. (Pubitemid 38159446)
5. Mallo M, Cervera J, Schanz J, et al. Impact of adjunct cytogenetic abnormalities for prognostic stratifi cation in patients wiThmyelodysplastic syndrome and deletion 5q. Leukemia 2011;25:110-120.
6. Giagounidis AAN, Germing U, Aul C. Biological and prognostic signifi cance of chromosome 5q deletions in myeloid malignancies. Clin Cancer Res 2006;12:5-10. (Pubitemid 43166169)
7. Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nature Rev Cancer 2004;4:314-322. (Pubitemid 38525287)
8. Kotla V, Goel S, Nischal S, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol 2009;2:36.
9. Vallet S, Palumbo A, Raje N, et al. Thalidomide and lenalidomide: mechanism-based potential drug combinations. Leuk Lymphoma 2008;49:1238-1245. (Pubitemid 352015786)
10. Quach H, Ritchie D, Stewart AK, et al. Mechanism of action of immunomodulatory drugs (IMiDs) in multiple myeloma. Leukemia 2010;24:22-32.
11. Galustian C, Meyer B, Labarthe M-C, et al. The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother 2009;58: 1033-1045.
12. Chang DH, Liu N, Klimek V, et al. Enhancement of liganddependent activation of human natural killer T cells by lenalidomide: Therapeutic implications. Blood 2006;108:618-621. (Pubitemid 44061362)
13. Fujii S, Shimizu K, Klimek V, et al. Severe and selective defi ciency of interferon-gamma-producing invariant natural killer T cells in patients wiThmyelodysplastic syndromes. Br J Haematol 2003;122: 617-622. (Pubitemid 36995216)
14. Chan AC, Neeson P, Leeansyah E, et al. Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients. Leukemia 2010;24:592-600.
15. Görgün G, Calabrese E, Soydan E, et al. Immunomodulatory eff ects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood 2010;116: 3227-3237.
16. Dredge K, Marriott JB, Macdonald CD, et al. Novel thalidomide analogues display anti-Angiogenic activity independently of immunomodulatory eff ects. Br J Cancer 2002;87:1166-1172. (Pubitemid 35418112)
17. Gandhi AK, Kang J, Naziruddin S, et al. Lenalidomide inhibits proliferation of Namalwa CSN.70 cells and interferes wiThGab1 phosphorylation and adaptor protein complex assembly. Leuk Res 2006;30:849-858. (Pubitemid 43816707)
18. Dredge K, Horsfall R, Robinson SP, et al. Orally administered lenalidomide (CC-5013) is anti-Angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc Res 2005;69:56-63. (Pubitemid 40410468)
19. Karin M. Nuclear factor-κB in cancer development and progression. Nature 2006;441:431-436. (Pubitemid 44050137)
20. Matsuoka A, Tochigi A, Kishimoto M, et al. Lenalidomide induces cell deaThin an MDS-derived cell line wiThdeletion of chromosome 5q by inhibition of cytokinesis. Leukemia 2010;24:748-755.
21. Richardson PG, Hindeshima T, Anderson KC. Bortezomib (PS-341): A novel, fi rst-in-class proteasome inhibitor for the treatment of multiple myeloma and other cancers. Cancer Control 2003;10:361-369. (Pubitemid 37296062)
22. Ebert BL, Galili N, Tamayo P, et al. An erythroid diff erentiation signature predicts response to lenalidomide in myelodysplastic syndrome. PLoS Med 2008;5:e35.
23. Jäd ersten M. Pathophysiology and treatment of the myelodysplastic syndrome wiThisolated 5q deletion. Haematologica 2010;95: 348-351.
24. List A, Dewald G, Bennett J, et al. Lenalidomide in the myelodysplastic syndrome wiThchromosome 5q deletion. N Engl J Med 2006; 355:1456-1465. (Pubitemid 44511560)
25. Adès L, Boehrer S, Prebet T, et al. Effi cacy and safety of lenalidomide in intermediate-2 or high-risk myelodysplastic syndromes wiTh5q deletion: Results of a phase 2 study. Blood 2009;113:3947-3952.
26. Raza A, Reeves JA, Feldman EJ, et al. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1-risk myelodysplastic syndromes wiThkaryotypes other than deletion 5q. Blood 2008; 111:86-93.
27. Kelaidi C, Eclache V, Fenaux P. The role of lenalidomide in the management of myelodysplasia wiThdel 5q. Br J Haematol 2008;140: 267-278.
28. Royer-Pokora B, Trost D, Mùller N, et al. Delineation by molecular cytogenetics of 5q deletion breakpoints in myelodysplastic syndromes and acute myeloid leukemia. Cancer Genet Cytogenet 2006;167:66-69.
29. Verstrepen L, Carpentier I, Verhelst K, et al. ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling. Biochem Pharmacol 2009;78:105-114.
30. Vereecke L, Beyaert R, van Loo G. The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends Immunol 2009;30:383-391.
31. Shembade N, Ma A, Harhaj EW. Inhibition of NF-κB signaling by A20 through disruption of ubiquitin enzyme complexes. Science 2010;327:1135-1139.
32. Sriskantharajah S, Ley SC. Turning off infl ammation signaling. Science 2010;327:1093-1094.
33. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nature Rev Genet 2010;11:597-610.
34. Starczynowski DT, Kuchenbauer F, Argiropoulos B, et al. Identifi cation of miR-145 and miR-146α as mediators of the 5qsyndrome phenotype. Nat Med 2010;16:49-58.
35. Taganov KD, Boldin MP, Chang KJ, et al. NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 2006;103:12481-12486. (Pubitemid 44267285)
36. O'N eill LA, Sheedy FJ, McCoy CE. Micro RNAs: The fi ne-tuners of Toll-like receptor signaling. Nat Rev Cancer 2011;11:163-175.
37. Starczynowski DT, Karsan A. Deregulation of innate immune signaling in myelodysplastic syndromes is associated wiThdeletion of chromosome arm 5q. Cell Cycle 2010;9:855-856.
38. Brigelius-Flohé R, Kipp A. Glutathione peroxidases in diff erent stages of carcinogenesis. Biochim Biophys Acta 2009;1790:1555-1568.
39. Irvine K, Stirling R, Hume D, et al. Rasputin, more promiscuous than ever; a review of G3BP. Int J Dev Biol 2004;48:1065-1077. (Pubitemid 40179573)
40. Vilàde Muga S, Timpson P, Cubells L, et al. Annexin A6 inhibits Ras signalling in breast cancer cells. Oncogene 2009;28:363-377.
41. Grewal T, Koese M, Rentero C, et al. Annexin A6-regulator of the EGFR/Ras signalling pathway and cholesterol homeostasis. Int J Biochem Cell Biol 2010;42:580-584.
42. Pierga J-Y, Reis-Filho JS, Cleator SJ, et al. Microarray-based comparative genomic hybridization of breast cancer patients receiving neoadjuvant chemotherapy. Br J Cancer 2007;96:341-351. (Pubitemid 46160641)
43. Loo LWM, Grove DI, Williams EM, et al. Array comparative genomic hybridization analysis of genomic alterations in breast cancer subtypes. Cancer Res 2004;64:8541-8549. (Pubitemid 39552066)
44. Wang Y, Sun X, Wu J, et al. Casein kinase 1αinteracts wiThRIP1 and regulates NF- κB activation. Biochemistry 2008;47:441-448.
45. Bidëre N, Ngo VN, Lee J, et al. Casein kinase 1 αgoverns antigenreceptor-induced NF- κB activation and human lymphoma cell survival. Nature 2009;458:92-96.
46. Deng J, Miller SA, Wang H-Y, et al. β-catenin interacts wiThand inhibits NF- κB in human colon and breast cancer. Cancer Cell 2002;2:323-334. (Pubitemid 41043966)
47. Beswick EJ, Reyes VE. CD74 in antigen presentation, infl ammation, and cancers of the gastrointestinal tract. World J Gastroenterol 2009;15:2855-2861.
48. Moseley TA, Haudenschild DR, Rose L, et al. Interleukin-17 family and IL-17 receptors. Cytok GrowThFact Rev 2003;14:155-174. (Pubitemid 36389528)
49. Hagemann T, Wilson J, Kulbe H, et al. Macrophages induce invasiveness of epithelial cancer cells via NF- κB and JNK. J Immunol 2005;175:1197-1205. (Pubitemid 41095008)
50. Braun T, Carvalho G, Coquelle A, et al. NF-κB constitutes a potential therapeutic target in high-risk myelodysplastic syndrome. Blood 2006;107:1156-1165. (Pubitemid 43156318)
51. Sanz C, Richard C, Prosper F, et al. Nuclear factor kappa B is activated in myelodysplastic bone marrow cells. Haematologica 2002;87:1005-1006.
52. Breccia M, Alimena G. NF-κB as a potential therapeutic target in myelodysplastic syndromes and acute myeloid leukemia. Expert Opin Ther. Targets 2010;14:1157-1176.
53. Bruserud Ø , Reikvam H. Therapeutic targeting of NF-κB in myelodysplastic syndromes and acute myeloid leukaemia - The biological heterogeneity. Expert Opin Ther. Targets 2010;14:1139-1142.
54. Harris TJC, Tepass U. Adherens junctions: from molecules to morphogenesis. Nature Rev Mol Cell Biol 2010;11:502-514.
55. Chlenski A, Cohn SL. Modulation of matrix remodeling by SPARC in neoplastic progression. Semin Cell Dev Biol 2010;21:55-65.
56. Murphy-Ullrich JE, Lane TF, Pallero MA, et al. SPARC mediates focal adhesion disassembly in endothelial cells through a follistatinlike region and the Ca(2 )-binding EF-hand. J Cell Biochem 1995; 57:341-350.
57. Yiu GK, Chan WY, Ng SW, et al. SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells. Am J Pathol 2001;159:609-622. (Pubitemid 32751091)
58. Francki A, McClure TD, Brekken RA, et al. SPARC regulates TGFbeta1-dependent signaling in primary glomerular mesangial cells. J Cell Biochem 2004;91:915-925.
59. Pellagatti A, J äd ersten M, Forsblom A-M, et al. Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q- syndrome patients. Proc Natl Acad Sci USA 2007;104:11406-11411. (Pubitemid 47175153)
60. Liu TX, Becker MW, Jelinek J, et al. Chromosome 5q deletion and epigenetic suppression of the gene encoding α-catenin ( CTNNA1 ) in myeloid cell transformation. Nat Med 2007;13:78-83. (Pubitemid 46067389)
61. Vasioukhin V, Bauer C, Degenstein L, et al. Hyperproliferation and defects in epithelial polarity upon conditional ablation of alphacatenin in skin. Cell 2001;104:605-617. (Pubitemid 32201954)
62. Goode BL, Eck MJ. Mechanism and function of formins in control of actin assembly. Annu Rev Biochem 2007;76:593-627.
63. Eisenmann KM, Dykema KJ, Matheson SF, et al. 5q- myelodysplastic syndromes: Chromosome 5q genes direct a tumor-suppression network sensing actin dynamics. Oncogene 2009;28:3429-3441.
64. Guettler S, Vartiainen MK, Miralles F, et al. RPEL motifs link the serum response factor cofactor MAL but not myocardin to Rho signaling via actin binding. Mol Cell Biol 2008;28:732-742.
65. Yusa A, Miyazaki K, Kimura N, et al. Epigenetic silencing of the sulfate transporter gene DTDST induces Sialyl Lewis x expression and accelerates proliferation of colon cancer cells. Cancer Res 2010;70: 4064-4073.
66. Tanoue T, Takeichi M. New insights into Fat cadherins. J Cell Sci 2005;118:2347-2353. (Pubitemid 40873074)
67. Matsui S, Utani A, Takahashi K, et al. Knockdown of Fat2 by siRNA inhibits the migration of human squamous carcinoma cells. J Dermatol Sci 2008;51:207-210.
68. Matsui S, Utani A, Takahashi K, et al. Human Fat2 is localized at immature adherens junctions in epidermal cells. J Dermatol Sci 2007;48:233-236. (Pubitemid 350026281)
69. Matsuda M, Yamashita JK, Tsukita S, et al. abLIM3 is a novel component of adherens junctions wiThactin-binding activity. Eur J Cell Biol 2010;89:807-816.
70. W u Y, Zhou BP. TNF-α/NF-κB / Snail pathway in cancer cell migration and invasion. Br J Cancer 2010;102:639-644.
71. Ebert BL, Pretz J, Bosco J, et al. Identifi cation of RPS14 as a 5qsyndrome gene by RNA interference screen. Nature 2008;451:335-339.
72. Barlow JL, Drynan LF, Hewett DR, et al. A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. Nat Med 2010;16:59-66.
73. Dutt S, Narla A, Lin K, et al. Haploinsuffi ciency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood 2011;117:2567-2576.
74. O'Dea EL, Kearns JD, Hoff mann A. UV as an amplifi er rather than inducer of NF-κB activity. Mol Cell 2008;30:632-641. (Pubitemid 351755056)
75. J ä d ersten M, Saft L, SmiThA, et al. T P53 mutations in low-risk myelodysplastic syndromes wiThdel(5q) predict disease progression. J Clin Oncol 2011;29:1971-1979.
76. Jäd ersten M, Saft L, Pellagatti A, et al. Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression. Haematologica 2009;94:1762-1766.
77. Boultwood J, Pellagatti A, Gattan H, et al. Gene expression profi ling of CD34- cells in patients wiThthe 5q- syndrome. Br J Haematol 2007;139:578-589.
78. Kittler R, Putz G, Pelletier L, et al. An endoribonuclease-prepared siRNA screen in human cells identifi es genes essential for cell division. Nature 2004;432:1036-1040. (Pubitemid 40052235)
79. Montaville P, Dai Y, Cheung CY, et al. Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22. Biochim Biophys Acta 2006;1763:1335-1343. (Pubitemid 44779864)
80. Sakai D, Trainor PA. Treacher Collins syndrome: unmasking the role of Tcof1/treacle. Int J Biochem Cell Biol 2009;41:1229-1232.
81. Crawford BE, Garner OB, Bishop JR, et al. Loss of the heparan sulfate sulfotransferase, Ndst1, in mammary epithelial cells selectively blocks lobuloalveolar development in mice. PLoS One 2010;5:e10691.
82. Bishop JR, Schuksz M, Esko JD. Heparan sulfate proteoglycyns fi ne-tune mammalian physiology. Nature 2007;446:1030-1037. (Pubitemid 46676065)
83. Arroyo JD, Hahn WC. Involvement of PP2A in viral and cellular transformation. Oncogene 2005;24:7746-7755. (Pubitemid 41670676)
84. Van Hoof C, Goris J. PP2A fulfi lls its promises as tumor suppressor: which subunits are important? Cancer Cell 2004;5: 105-106.
85. Mumby M. PP2A: unveiling a reluctant tumor suppressor. Cell 2007;130:21-24. (Pubitemid 47031327)
86. Boutros R, Lobjois V, Ducommun B. CDC25 phosphatases in cancer cells: Key players? Good targets? Nat Rev Cancer 2007;7:495-507. (Pubitemid 46985396)
87. Margolis SS, Perry JA, Forester CM, et al. Role for the PP2A/B56? phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis. Cell 2006;127:759-773. (Pubitemid 44781028)
88. Wei S, Chen X, Rocha K, et al. A critical role for phosphatase haplodefi ciency in the selective suppression of deletion 5q MDS by lenalidomide. Proc Natl Acad Sci USA 2009;106:12974-12979.
89. X u N, Papagiannakopoulos T, Pan G, et al. Micro RNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 2009;137:647-658.
90. Mallanna SK, Rizzino A. Emerging roles of microRNAs in the control of embryonic stem cells and the generation of induced pluripotent stem cells. Dev Biol 2010;344:16-25.
91. Y u J, Baron V, Mercola D, et al. A network of p73, p53 and Egr1 is required for effi cient apoptosis in tumor cells. Cell DeaThDiff er 2007;14:436-446.
92. Wilson A, Laurenti E, Trumpp A. Balancing dormant and self-renewing hematopoietic stem cells. Curr Opin Genet Dev 2009;19:461-468.
93. Tehranchi R, Woll PS, Anderson K, et al. Persistent malignant stem cells in del(5q) myelodysplasia in remission. N Engl J Med 2010;363:1025-1037.
94. Sawanobori M, Yamaguchi S, Hasegawa M, et al. Expression of TNF receptors and related signaling molecules in the bone marrow from patients wiThmyelodysplastic syndromes. Leuk Res 2003;27:583-591. (Pubitemid 36398093)
95. Kerbauy DB, Deeg HJ. Apoptosis and antiapoptotic mechanisms in the progression of myelodysplastic syndrome. Exp Hematol 2007;35:1739-1746. (Pubitemid 47633781)
96. Grosjean-Raillard J, Tailler M, Ad ès L, et al. ATM mediates constitutive NF-κB activation in high-risk myelodysplastic syndrome and acute myeloid leukemia. Oncogene 2009;28:1099-1109.
97. Sun Y, Cook JR. Fluorescence in situ hybridization for del (5q) in myelodysplasia/acute myeloid leukemia: Comparison of EGR1 vs. CSF1R probes and diagnostic yield over metaphase cytogenetics alone. Leuk Res 2010;34:340-343.
98. Böl l B, Borchmann P, Topp MS, et al. Lenalidomide in patients wiThrefractory or multiple relapsed Hodgkin lymphoma. Br J Haematol 2009;148:480-482.
99. Corazzelli G, De Filippi R, Capobianco G, et al. Tumor fl are reactions and response to lenalidomide in patients wiThrefractory classic Hodgkin lymphoma. Am J Hematol 2010;85:87-90.
100. Habermann TM, Lossos IS, Justice G, et al. Lenalidomide oral monotherapy produces a high response rate in patients wiThrelapsed or refractory mantle cell lymphoma. Br J Haematol 2009;145:344-349.
101. Wiernik PH, Lossos IS, Tuscano JM, et al. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol 2008;26:4952-4957.
102. Witzig TE, Wiernik PH, Moore T, et al. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's lymphoma. J Clin Oncol 2009;27:5404-5409.
103. Staudt LM. Oncogenic activation of NF-κB . Cold Spring Harb Perspect Biol 2010;2:a000109.
104. Schmitz R, Hansmann ML, Bohle V, et al. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J Exp Med 2009;206:981-989.
105. Terpos E, Verrou E, Banti A, et al. Bortezomib is an eff ective agent for MDS/MPD syndrome wiTh5q- anomaly and thrombocytosis. Leukemia Res 2007;31:559-562. (Pubitemid 46198932)
106. Liesveld JL, Rosell KE, Bechelli J, et al. Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines. Cancer Invest 2011;29:439-450.
107. Messa E, Carturan S, Maff èC, et al. Deferasirox is a powerful NF-κB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging. Haematologica 2010;95: 1308-1316.