A critical review of the molecular pathophysiology of lenalidomide sensitivity in 5q − myelodysplastic syndromes

References

• Ebert BL. Deletion 5q in myelodysplastic syndrome: a paradigm for the study of hemizygous deletions in cancer. Leukemia 2009;23:1252–1256.
   PubMed Web of Science ®Google Scholar
• Boultwood J, Fidler C, Strickson AJ, . Narrowing and genomic annotation of the commonly deleted region of the 5q- syndrome. Blood 2002;99:4638–4641.
   PubMed Web of Science ®Google Scholar
• Barlow JL, Drynan LF, Trim NL, . New insights into 5q- syndrome as a ribosomopathy. Cell Cycle 2010;9:4286–4293.
   PubMed Web of Science ®Google Scholar
• Giagounidis AAN, Germing U, Haase S, . Clinical, morphological, cytogenetic, and prognostic features of patients with myelodysplastic syndromes and del(5q) including band q31. Leukemia 2004;18:113–119.
   PubMed Web of Science ®Google Scholar
• Mallo M, Cervera J, Schanz J, . Impact of adjunct cytogenetic abnormalities for prognostic stratification in patients with myelodysplastic syndrome and deletion 5q. Leukemia 2011;25:110–120.
   PubMed Web of Science ®Google Scholar
• Giagounidis AAN, Germing U, Aul C. Biological and prognostic significance of chromosome 5q deletions in myeloid malignancies. Clin Cancer Res 2006;12:5–10.
   PubMed Web of Science ®Google Scholar
• Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nature Rev Cancer 2004;4:314–322.
   PubMed Web of Science ®Google Scholar
• Kotla V, Goel S, Nischal S, . Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol 2009;2:36.
   PubMed Web of Science ®Google Scholar
• Vallet S, Palumbo A, Raje N, . Thalidomide and lenalidomide: mechanism-based potential drug combinations. Leuk Lymphoma 2008;49:1238–1245.
   PubMed Web of Science ®Google Scholar
• Quach H, Ritchie D, Stewart AK, . Mechanism of action of immunomodulatory drugs (IMiDs) in multiple myeloma. Leukemia 2010;24:22–32.
   PubMed Web of Science ®Google Scholar
• Galustian C, Meyer B, Labarthe M-C, . The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother 2009;58: 1033–1045.
   PubMed Web of Science ®Google Scholar
• Chang DH, Liu N, Klimek V, . Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications. Blood 2006;108:618–621.
   PubMed Web of Science ®Google Scholar
• Fujii S, Shimizu K, Klimek V, . Severe and selective deficiency of interferon-gamma-producing invariant natural killer T cells in patients with myelodysplastic syndromes. Br J Haematol 2003;122: 617–622.
   PubMed Web of Science ®Google Scholar
• Chan AC, Neeson P, Leeansyah E, . Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients. Leukemia 2010;24:592–600.
   PubMed Web of Science ®Google Scholar
• Görgün G, Calabrese E, Soydan E, . Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood 2010;116: 3227–3237.
   PubMed Web of Science ®Google Scholar
• Dredge K, Marriott JB, Macdonald CD, . Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Br J Cancer 2002;87:1166–1172.
   PubMed Web of Science ®Google Scholar
• Gandhi AK, Kang J, Naziruddin S, . Lenalidomide inhibits proliferation of Namalwa CSN.70 cells and interferes with Gab1 phosphorylation and adaptor protein complex assembly. Leuk Res 2006;30:849–858.
   PubMed Web of Science ®Google Scholar
• Dredge K, Horsfall R, Robinson SP, . 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.
   PubMed Web of Science ®Google Scholar
• Karin M. Nuclear factor-κB in cancer development and progression. Nature 2006;441:431–436.
   PubMed Web of Science ®Google Scholar
• Matsuoka A, Tochigi A, Kishimoto M, . Lenalidomide induces cell death in an MDS-derived cell line with deletion of chromosome 5q by inhibition of cytokinesis. Leukemia 2010;24:748–755.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Hindeshima T, Anderson KC. Bortezomib (PS-341): a novel, first-in-class proteasome inhibitor for the treatment of multiple myeloma and other cancers. Cancer Control 2003;10:361–369.
   PubMedGoogle Scholar
• Ebert BL, Galili N, Tamayo P, . An erythroid differentiation signature predicts response to lenalidomide in myelodysplastic syndrome. PLoS Med 2008;5:e35.
   PubMed Web of Science ®Google Scholar
• Jädersten M. Pathophysiology and treatment of the myelodysplastic syndrome with isolated 5q deletion. Haematologica 2010;95: 348–351.
   PubMed Web of Science ®Google Scholar
• List A, Dewald G, Bennett J, . Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 2006; 355:1456–1465.
   PubMed Web of Science ®Google Scholar
• Adès L, Boehrer S, Prebet T, . Efficacy and safety of lenalidomide in intermediate-2 or high-risk myelodysplastic syndromes with 5q deletion: results of a phase 2 study. Blood 2009;113:3947–3952.
   PubMed Web of Science ®Google Scholar
• Raza A, Reeves JA, Feldman EJ, . Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1-risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood 2008; 111:86–93.
   PubMed Web of Science ®Google Scholar
• Kelaidi C, Eclache V, Fenaux P. The role of lenalidomide in the management of myelodysplasia with del 5q. Br J Haematol 2008;140: 267–278.
   PubMed Web of Science ®Google Scholar
• Royer-Pokora B, Trost D, Müller N, . Delineation by molecular cytogenetics of 5q deletion breakpoints in myelodysplastic syndromes and acute myeloid leukemia. Cancer Genet Cytogenet 2006;167:66–69.
   PubMed Web of Science ®Google Scholar
• Verstrepen L, Carpentier I, Verhelst K, . ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling. Biochem Pharmacol 2009;78:105–114.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Shembade N, Ma A, Harhaj EW. Inhibition of NF-κB signaling by A20 through disruption of ubiquitin enzyme complexes. Science 2010;327:1135–1139.
   PubMed Web of Science ®Google Scholar
• Sriskantharajah S, Ley SC. Turning off inflammation signaling. Science 2010;327:1093–1094.
   PubMed Web of Science ®Google Scholar
• Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nature Rev Genet 2010;11:597–610.
   PubMed Web of Science ®Google Scholar
• Starczynowski DT, Kuchenbauer F, Argiropoulos B, . Identification of miR-145 and miR-146α as mediators of the 5q- syndrome phenotype. Nat Med 2010;16:49–58.
   PubMed Web of Science ®Google Scholar
• Taganov KD, Boldin MP, Chang KJ, . 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.
   PubMed Web of Science ®Google Scholar
• O'Neill LA, Sheedy FJ, McCoy CE. Micro RNAs: the fine-tuners of Toll-like receptor signaling. Nat Rev Cancer 2011;11:163–175.
   Web of Science ®Google Scholar
• Starczynowski DT, Karsan A. Deregulation of innate immune signaling in myelodysplastic syndromes is associated with deletion of chromosome arm 5q. Cell Cycle 2010;9:855–856.
   PubMed Web of Science ®Google Scholar
• Brigelius-Flohé R, Kipp A. Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta 2009;1790:1555–1568.
   PubMed Web of Science ®Google Scholar
• Irvine K, Stirling R, Hume D, . Rasputin, more promiscuous than ever; a review of G3BP. Int J Dev Biol 2004;48:1065–1077.
   PubMed Web of Science ®Google Scholar
• Vilà de Muga S, Timpson P, Cubells L, . Annexin A6 inhibits Ras signalling in breast cancer cells. Oncogene 2009;28:363–377.
   PubMed Web of Science ®Google Scholar
• Grewal T, Koese M, Rentero C, . Annexin A6-regulator of the EGFR/Ras signalling pathway and cholesterol homeostasis. Int J Biochem Cell Biol 2010;42:580–584.
   PubMed Web of Science ®Google Scholar
• Pierga J-Y, Reis-Filho JS, Cleator SJ, . Microarray-based comparative genomic hybridization of breast cancer patients receiving neoadjuvant chemotherapy. Br J Cancer 2007;96:341–351.
   PubMed Web of Science ®Google Scholar
• Loo LWM, Grove DI, Williams EM, . Array comparative genomic hybridization analysis of genomic alterations in breast cancer subtypes. Cancer Res 2004;64:8541–8549.
   PubMed Web of Science ®Google Scholar
• Wang Y, Sun X, Wu J, . Casein kinase 1α interacts with RIP1 and regulates NF-κB activation. Biochemistry 2008;47:441–448.
   PubMed Web of Science ®Google Scholar
• Bidère N, Ngo VN, Lee J, . Casein kinase 1α governs antigen-receptor-induced NF-κB activation and human lymphoma cell survival. Nature 2009;458:92–96.
   PubMed Web of Science ®Google Scholar
• Deng J, Miller SA, Wang H-Y, . Β-catenin interacts with and inhibits NF-κB in human colon and breast cancer. Cancer Cell 2002;2:323–334.
   PubMed Web of Science ®Google Scholar
• Beswick EJ, Reyes VE. CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract. World J Gastroenterol 2009;15:2855–2861.
   PubMed Web of Science ®Google Scholar
• Moseley TA, Haudenschild DR, Rose L, . Interleukin-17 family and IL-17 receptors. Cytok Growth Fact Rev 2003;14:155–174.
   PubMed Web of Science ®Google Scholar
• Hagemann T, Wilson J, Kulbe H, . Macrophages induce invasiveness of epithelial cancer cells via NF-κB and JNK. J Immunol 2005;175:1197–1205.
   PubMed Web of Science ®Google Scholar
• Braun T, Carvalho G, Coquelle A, . NF-κB constitutes a potential therapeutic target in high-risk myelodysplastic syndrome. Blood 2006;107:1156–1165.
   PubMed Web of Science ®Google Scholar
• Sanz C, Richard C, Prosper F, . Nuclear factor kappa B is activated in myelodysplastic bone marrow cells. Haematologica 2002;87:1005–1006.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Harris TJC, Tepass U. Adherens junctions: from molecules to morphogenesis. Nature Rev Mol Cell Biol 2010;11:502–514.
   PubMed Web of Science ®Google Scholar
• Chlenski A, Cohn SL. Modulation of matrix remodeling by SPARC in neoplastic progression. Semin Cell Dev Biol 2010;21:55–65.
   PubMed Web of Science ®Google Scholar
• Murphy-Ullrich JE, Lane TF, Pallero MA, . SPARC mediates focal adhesion disassembly in endothelial cells through a follistatin-like region and the Ca(2+)-binding EF-hand. J Cell Biochem 1995; 57:341–350.
   PubMed Web of Science ®Google Scholar
• Yiu GK, Chan WY, Ng SW, . SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells. Am J Pathol 2001;159:609–622.
   Google Scholar
• Francki A, McClure TD, Brekken RA, . SPARC regulates TGF-beta1-dependent signaling in primary glomerular mesangial cells. J Cell Biochem 2004;91:915–925.
   PubMed Web of Science ®Google Scholar
• Pellagatti A, Jädersten M, Forsblom A-M, . 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.
   PubMed Web of Science ®Google Scholar
• Liu TX, Becker MW, Jelinek J, . Chromosome 5q deletion and epigenetic suppression of the gene encoding α-catenin (CTNNA1) in myeloid cell transformation. Nat Med 2007;13:78–83.
   PubMed Web of Science ®Google Scholar
• Vasioukhin V, Bauer C, Degenstein L, . Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin. Cell 2001;104:605–617.
   PubMed Web of Science ®Google Scholar
• Goode BL, Eck MJ. Mechanism and function of formins in control of actin assembly. Annu Rev Biochem 2007;76:593–627.
   PubMed Web of Science ®Google Scholar
• Eisenmann KM, Dykema KJ, Matheson SF, . 5q- myelodysplastic syndromes: chromosome 5q genes direct a tumor-suppression network sensing actin dynamics. Oncogene 2009;28:3429–3441.
   PubMed Web of Science ®Google Scholar
• Guettler S, Vartiainen MK, Miralles F, . 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.
   PubMedGoogle Scholar
• Yusa A, Miyazaki K, Kimura N, . Epigenetic silencing of the sulfate transporter gene DTDST induces Sialyl Lewisx expression and accelerates proliferation of colon cancer cells. Cancer Res 2010;70: 4064–4073.
   PubMed Web of Science ®Google Scholar
• Tanoue T, Takeichi M. New insights into Fat cadherins. J Cell Sci 2005;118:2347–2353.
   PubMed Web of Science ®Google Scholar
• Matsui S, Utani A, Takahashi K, . Knockdown of Fat2 by siRNA inhibits the migration of human squamous carcinoma cells. J Dermatol Sci 2008;51:207–210.
   PubMed Web of Science ®Google Scholar
• Matsui S, Utani A, Takahashi K, . Human Fat2 is localized at immature adherens junctions in epidermal cells. J Dermatol Sci 2007;48:233–236.
   PubMed Web of Science ®Google Scholar
• Matsuda M, Yamashita JK, Tsukita S, . abLIM3 is a novel component of adherens junctions with actin-binding activity. Eur J Cell Biol 2010;89:807–816.
   PubMed Web of Science ®Google Scholar
• Wu Y, Zhou BP. TNF-α/NF-κB/ Snail pathway in cancer cell migration and invasion. Br J Cancer 2010;102:639–644.
   PubMed Web of Science ®Google Scholar
• Ebert BL, Pretz J, Bosco J, . Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature 2008;451:335–339.
   PubMed Web of Science ®Google Scholar
• Barlow JL, Drynan LF, Hewett DR, . A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. Nat Med 2010;16:59–66.
   PubMed Web of Science ®Google Scholar
• Dutt S, Narla A, Lin K, . Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood 2011;117:2567–2576.
   PubMed Web of Science ®Google Scholar
• O'Dea EL, Kearns JD, Hoffmann A. UV as an amplifier rather than inducer of NF-κB activity. Mol Cell 2008;30:632–641.
   PubMed Web of Science ®Google Scholar
• Jädersten M, Saft L, Smith A, . TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol 2011;29:1971–1979.
   PubMed Web of Science ®Google Scholar
• Jädersten M, Saft L, Pellagatti A, . Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression. Haematologica 2009;94:1762–1766.
   PubMed Web of Science ®Google Scholar
• Boultwood J, Pellagatti A, Gattan H, . Gene expression profiling of CD34+cells in patients with the 5q- syndrome. Br J Haematol 2007;139:578–589.
   PubMed Web of Science ®Google Scholar
• Kittler R, Putz G, Pelletier L, . An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division. Nature 2004;432:1036–1040.
   PubMed Web of Science ®Google Scholar
• Montaville P, Dai Y, Cheung CY, . Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22. Biochim Biophys Acta 2006;1763:1335–1343.
   PubMed Web of Science ®Google Scholar
• Sakai D, Trainor PA. Treacher Collins syndrome: unmasking the role of Tcof1/treacle. Int J Biochem Cell Biol 2009;41:1229–1232.
   PubMed Web of Science ®Google Scholar
• Crawford BE, Garner OB, Bishop JR, . Loss of the heparan sulfate sulfotransferase, Ndst1, in mammary epithelial cells selectively blocks lobuloalveolar development in mice. PLoS One 2010;5:e10691.
   Google Scholar
• Bishop JR, Schuksz M, Esko JD. Heparan sulfate proteoglycyns fine-tune mammalian physiology. Nature 2007;446:1030–1037.
   PubMed Web of Science ®Google Scholar
• Arroyo JD, Hahn WC. Involvement of PP2A in viral and cellular transformation. Oncogene 2005;24:7746–7755.
   PubMedGoogle Scholar
• Van Hoof C, Goris J. PP2A fulfills its promises as tumor suppressor: which subunits are important? Cancer Cell 2004;5: 105–106.
   PubMed Web of Science ®Google Scholar
• Mumby M. PP2A: unveiling a reluctant tumor suppressor. Cell 2007;130:21–24.
   PubMed Web of Science ®Google Scholar
• Boutros R, Lobjois V, Ducommun B. CDC25 phosphatases in cancer cells: key players? Good targets? Nat Rev Cancer 2007;7:495–507.
   PubMed Web of Science ®Google Scholar
• Margolis SS, Perry JA, Forester CM, . Role for the PP2A/B56δ phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis. Cell 2006;127:759–773.
   PubMed Web of Science ®Google Scholar
• Wei S, Chen X, Rocha K, . A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide. Proc Natl Acad Sci USA 2009;106:12974–12979.
   PubMed Web of Science ®Google Scholar
• Xu N, Papagiannakopoulos T, Pan G, . Micro RNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 2009;137:647–658.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Yu J, Baron V, Mercola D, . A network of p73, p53 and Egr1 is required for efficient apoptosis in tumor cells. Cell Death Differ 2007;14:436–446.
   PubMed Web of Science ®Google Scholar
• Wilson A, Laurenti E, Trumpp A. Balancing dormant and self-renewing hematopoietic stem cells. Curr Opin Genet Dev 2009;19:461–468.
   PubMed Web of Science ®Google Scholar
• Tehranchi R, Woll PS, Anderson K, . Persistent malignant stem cells in del(5q) myelodysplasia in remission. N Engl J Med 2010;363:1025–1037.
   PubMed Web of Science ®Google Scholar
• Sawanobori M, Yamaguchi S, Hasegawa M, . Expression of TNF receptors and related signaling molecules in the bone marrow from patients with myelodysplastic syndromes. Leuk Res 2003;27:583–591.
   PubMed Web of Science ®Google Scholar
• Kerbauy DB, Deeg HJ. Apoptosis and antiapoptotic mechanisms in the progression of myelodysplastic syndrome. Exp Hematol 2007;35:1739–1746.
   PubMed Web of Science ®Google Scholar
• Grosjean-Raillard J, Tailler M, Adès L, . ATM mediates constitutive NF-κB activation in high-risk myelodysplastic syndrome and acute myeloid leukemia. Oncogene 2009;28:1099–1109.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Böll B, Borchmann P, Topp MS, . Lenalidomide in patients with refractory or multiple relapsed Hodgkin lymphoma. Br J Haematol 2009;148:480–482.
   PubMed Web of Science ®Google Scholar
• Corazzelli G, De Filippi R, Capobianco G, . Tumor flare reactions and response to lenalidomide in patients with refractory classic Hodgkin lymphoma. Am J Hematol 2010;85:87–90.
   PubMed Web of Science ®Google Scholar
• Habermann TM, Lossos IS, Justice G, . Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol 2009;145:344–349.
   PubMed Web of Science ®Google Scholar
• Wiernik PH, Lossos IS, Tuscano JM, . Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol 2008;26:4952–4957.
   PubMed Web of Science ®Google Scholar
• Witzig TE, Wiernik PH, Moore T, . Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's lymphoma. J Clin Oncol 2009;27:5404–5409.
   PubMed Web of Science ®Google Scholar
• Staudt LM. Oncogenic activation of NF-κB. Cold Spring Harb Perspect Biol 2010;2:a000109.
   PubMed Web of Science ®Google Scholar
• Schmitz R, Hansmann ML, Bohle V, . TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J Exp Med 2009;206:981–989.
   PubMed Web of Science ®Google Scholar
• Terpos E, Verrou E, Banti A, . Bortezomib is an effective agent for MDS/MPD syndrome with 5q- anomaly and thrombocytosis. Leukemia Res 2007;31:559–562.
   PubMed Web of Science ®Google Scholar
• Liesveld JL, Rosell KE, Bechelli J, . Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines. Cancer Invest 2011;29:439–450.
   PubMed Web of Science ®Google Scholar
• Messa E, Carturan S, Maffè C, . 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.
   PubMed Web of Science ®Google Scholar