Review Article
The therapeutic potential of the proteasome in leukaemia†
Scott Marshall McCloskey,
Mary Frances McMullin,
Brian Walker,
Alexandra E Irvine,
Corresponding Author
Scott Marshall McCloskey
CCRCB, Queen's University of Belfast, Belfast, Northern Ireland
CCRCB, Queen's University of Belfast, G Floor, Belfast, Northern Ireland.Search for more papers by this authorMary Frances McMullin
Department of Haematology, Queen's University of Belfast, Belfast, Northern Ireland
Search for more papers by this authorBrian Walker
School of Pharmacy, Queen's University of Belfast, Belfast, Northern Ireland
Search for more papers by this authorAlexandra E Irvine
CCRCB, Queen's University of Belfast, Belfast, Northern Ireland
Search for more papers by this authorScott Marshall McCloskey,
Mary Frances McMullin,
Brian Walker,
Alexandra E Irvine,
Corresponding Author
Scott Marshall McCloskey
CCRCB, Queen's University of Belfast, Belfast, Northern Ireland
CCRCB, Queen's University of Belfast, G Floor, Belfast, Northern Ireland.Search for more papers by this authorMary Frances McMullin
Department of Haematology, Queen's University of Belfast, Belfast, Northern Ireland
Search for more papers by this authorBrian Walker
School of Pharmacy, Queen's University of Belfast, Belfast, Northern Ireland
Search for more papers by this authorAlexandra E Irvine
CCRCB, Queen's University of Belfast, Belfast, Northern Ireland
Search for more papers by this author†
There have been no other submissions of this review or duplications of this work. There are no conflicts of interest. This manuscript is a review of already published and ethically approved research.
Abstract
Many cellular processes converge on the proteasome, and its key regulatory role is increasingly being recognized. Proteasome inhibition allows the manipulation of many cellular pathways including apoptotic and cell cycle mechanisms. The proteasome inhibitor bortezomib has enhanced responses in newly diagnosed patients with myeloma and provides a new line of therapy in relapsed and refractory patients. Malignant cells are more sensitive to proteasome inhibition than normal haematopoietic cells. Proteasome inhibition enhances many conventional therapies and its role in leukaemia is promising. Copyright © 2008 John Wiley & Sons, Ltd.
References
- 1 Reed SI. The ubiquitin-proteasome pathway in cell cycle control. Results Probl Cell Differ 2006; 42: 147–181.
- 2 Hershko A. Ubiquitin: roles in protein modification and breakdown. Cell 1983; 34(1): 11–12.
- 3 Chen Z, Pickart CMA. 25-kilodalton ubiquitin carrier protein (E2) catalyzes multi-ubiquitin chain synthesis via lysine 48 of ubiquitin. J Biol Chem 1990; 265(35): 21835–21842.
- 4 Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 2002; 82(2): 373–428.
- 5 Reed SH, Gillette TG. Nucleotide excision repair and the ubiquitin proteasome pathway—do all roads lead to Rome? DNA Repair (Amst) 2007; 6(2): 149–156.
- 6 Wang WH. Regulation of ROMK (Kir1.1) channels: new mechanisms and aspects. Am J Physiol Renal Physiol 2006; 290(1): F14–F19.
- 7 d'Azzo A, Bongiovanni A, Nastasi T. E3 ubiquitin ligases as regulators of membrane protein trafficking and degradation. Traffic 2005; 6(6): 429–441.
- 8 Amerik AY, Hochstrasser M. Mechanism and function of deubiquitinating enzymes. Biochim Biophys Acta 2004; 1695(1–3): 189–207.
- 9 Gillette TG, Yu S, Zhou Z, Waters R, Johnston SA, Reed SH. Distinct functions of the ubiquitin-proteasome pathway influence nucleotide excision repair. EMBO J 2006; 25(11): 2529–2538.
- 10 Demartino GN, Gillette TG. Proteasomes: machines for all reasons. Cell 2007; 129(4): 659–662.
- 11 Groll M, Heinemeyer W, Jager S, et al. The catalytic sites of 20S proteasomes and their role in subunit maturation: a mutational and crystallographic study. Proc Natl Acad Sci USA 1999; 96(20): 10976–10983.
- 12 Pickart CM, Cohen RE. Proteasomes and their kin: proteases in the machine age. Nat Rev Mol Cell Biol 2004; 5(3): 177–187.
- 13 Bochtler M, Ditzel L, Groll M, Hartmann C, Huber R. The proteasome. Annu Rev Biophys Biomol Struct 1999; 28: 295–317.
- 14 Coux O, Tanaka K, Goldberg AL. Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem 1996; 65: 801–847.
- 15 Dahlmann B, Ruppert T, Kloetzel PM, Kuehn L. Subtypes of 20S proteasomes from skeletal muscle. Biochimie 2001; 83(3–4): 295–299.
- 16 Strehl B, Seifert U, Kruger E, Heink S, Kuckelkorn U, Kloetzel PM. Interferon-gamma, the functional plasticity of the ubiquitin-proteasome system, and MHC class I antigen processing. Immunol Rev 2005; 207: 19–30.
- 17 Shibatani T, Carlson EJ, Larabee F, McCormack AL, Fruh K, Skach WR. Global organization and function of mammalian cytosolic proteasome pools: implications for PA28 and 19S regulatory complexes. Mol Biol Cell 2006; 17(12): 4962–4971.
- 18 Goldberg AL, Cascio P, Saric T, Rock KL. The importance of the proteasome and subsequent proteolytic steps in the generation of antigenic peptides. Mol Immunol 2002; 39(3–4): 147–164.
- 19 Naujokat C, Fuchs D, Berges C. Adaptive modification and flexibility of the proteasome system in response to proteasome inhibition. Biochim Biophys Acta 2007; 1773(9): 1389–1397.
- 20 Eleuteri AM, Kohanski RA, Cardozo C, Orlowski M. Bovine spleen multicatalytic proteinase complex (proteasome). Replacement of X, Y, and Z subunits by LMP7, LMP2, and MECL1 and changes in properties and specificity. J Biol Chem 1997; 272(18): 11824–11831.
- 21 Yuan X, Miller M, Belote JM. Duplicated proteasome subunit genes in Drosophila melanogaster encoding testes-specific isoforms. Genetics 1996; 144(1): 147–157.
- 22 Mason GG, Hendil KB, Rivett AJ. Phosphorylation of proteasomes in mammalian cells. Identification of two phosphorylated subunits and the effect of phosphorylation on activity. Eur J Biochem 1996; 238(2): 453–462.
- 23 Wehren A, Meyer HE, Sobek A, Kloetzel PM, Dahlmann B. Phosphoamino acids in proteasome subunits. Biol Chem 1996; 377(7–8): 497–503.
- 24 Kimura Y, Takaoka M, Tanaka S, et al. N(alpha)-acetylation and proteolytic activity of the yeast 20 S proteasome. J Biol Chem 2000; 275(7): 4635–4639.
- 25 Bose S, Stratford FL, Broadfoot KI, Mason GG, Rivett AJ. Phosphorylation of 20S proteasome alpha subunit C8 (alpha7) stabilizes the 26S proteasome and plays a role in the regulation of proteasome complexes by gamma-interferon. Biochem J 2004; 378(Pt 1): 177–184.
- 26 Sumegi M, Hunyadi-Gulyas E, Medzihradszky KF, Udvardy A. 26S proteasome subunits are O-linked N-acetylglucosamine- modified in Drosophila melanogaster. Biochem Biophys Res Commun 2003; 312(4): 1284–1289.
- 27 Glickman MH, Raveh D. Proteasome plasticity. FEBS Lett 2005; 579(15): 3214–3223.
- 28 Schmidt F, Dahlmann B, Janek K, et al. Comprehensive quantitative proteome analysis of 20S proteasome subtypes from rat liver by isotope coded affinity tag and 2-D gel-based approaches. Proteomics 2006; 6(16): 4622–4632.
- 29 Lecker SH, Goldberg AL, Mitch WE. Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. J Am Soc Nephrol 2006; 17(7): 1807–1819.
- 30 Genini D, Catapano CV. Block of nuclear receptor ubiquitination. A mechanism of ligand-dependent control of peroxisome proliferator-activated receptor delta activity. J Biol Chem 2007; 282(16): 11776–11785.
- 31 Grillari J, Katinger H, Voglauer R. Aging and the ubiquitinome: traditional and non-traditional functions of ubiquitin in aging cells and tissues. Exp Gerontol 2006; 41(11): 1067–1079.
- 32 Amati B, Sanchez-Arevalo Lobo VJ. MYC degradation: deubiquitinating enzymes enter the dance. Nat Cell Biol 2007; 9(7): 729–731.
- 33 Meray RK, Lansbury PT Jr. Reversible monoubiquitination regulates the Parkinson disease-associated ubiquitin hydrolase UCH-L1. J Biol Chem 2007; 282(14): 10567–10575.
- 34 Hanna J, Meides A, Zhang DP, Finley D. A ubiquitin stress response induces altered proteasome composition. Cell 2007; 129(4): 747–759.
- 35 Farout L, Mary J, Vinh J, Szweda LI, Friguet B. Inactivation of the proteasome by 4-hydroxy-2-nonenal is site specific and dependant on 20S proteasome subtypes. Arch Biochem Biophys 2006; 453(1): 135–142.
- 36 Merforth S, Kuehn L, Osmers A, Dahlmann B. Alteration of 20S proteasome-subtypes and proteasome activator PA28 in skeletal muscle of rat after induction of diabetes mellitus. Int J Biochem Cell Biol 2003; 35(5): 740–748.
- 37 Palmer A, Rivett AJ, Thomson S, et al. Subpopulations of proteasomes in rat liver nuclei, microsomes and cytosol. Biochem J 1996; 316(Pt 2): 401–407.
- 38 Cardozo C, Kohanski RA. Altered properties of the branched chain amino acid-preferring activity contribute to increased cleavages after branched chain residues by the “immunoproteasome”. J Biol Chem 1998; 273(27): 16764–16770.
- 39 Rechsteiner M, Hill CP. Mobilizing the proteolytic machine: cell biological roles of proteasome activators and inhibitors. Trends Cell Biol 2005; 15(1): 27–33.
- 40 Khor B, Bredemeyer AL, Huang CY, et al. Proteasome activator PA200 is required for normal spermatogenesis. Mol Cell Biol 2006; 26(8): 2999–3007.
- 41 Zaiss DM, Standera S, Kloetzel PM, Sijts AJ. PI31 is a modulator of proteasome formation and antigen processing. Proc Natl Acad Sci USA 2002; 99(22): 14344–14349.
- 42 Gaczynska M, Osmulski PA, Gao Y, Post MJ, Simons M. Proline- and arginine-rich peptides constitute a novel class of allosteric inhibitors of proteasome activity. Biochemistry 2003; 42(29): 8663–8670.
- 43 Keller JN, Hanni KB, Markesbery WR. Impaired proteasome function in Alzheimer's disease. J Neurochem 2000; 75(1): 436–439.
- 44 Oh S, Hong HS, Hwang E, et al. Amyloid peptide attenuates the proteasome activity in neuronal cells. Mech Ageing Dev 2005; 126(12): 1292–1299.
- 45 Keck S, Nitsch R, Grune T, Ullrich O. Proteasome inhibition by paired helical filament-tau in brains of patients with Alzheimer's disease. J Neurochem 2003; 85(1): 115–122.
- 46 Almeida CG, Takahashi RH, Gouras GK. Beta-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system. J Neurosci 2006; 26(16): 4277–4288.
- 47 Gillardon F, Kloss A, Berg M, et al. The 20S proteasome isolated from Alzheimer's disease brain shows post-translational modifications but unchanged proteolytic activity. J Neurochem 2007; 101: 1483–1490.
- 48 Bulteau AL, Lundberg KC, Humphries KM, et al. Oxidative modification and inactivation of the proteasome during coronary occlusion/reperfusion. J Biol Chem 2001; 276(32): 30057–30063.
- 49 Fribley A, Zeng Q, Wang CY. Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Mol Cell Biol 2004; 24(22): 9695–9704.
- 50 Dasmahapatra G, Nguyen TK, Dent P, Grant S. Adaphostin and bortezomib induce oxidative injury and apoptosis in imatinib mesylate-resistant hematopoietic cells expressing mutant forms of Bcr/Abl. Leuk Res 2006; 30(10): 1263–1272.
- 51 Dasmahapatra G, Rahmani M, Dent P, Grant S. The tyrphostin adaphostin interacts synergistically with proteasome inhibitors to induce apoptosis in human leukemia cells through a reactive oxygen species (ROS)-dependent mechanism. Blood 2006; 107(1): 232–240.
- 52 Strauss SJ, Higginbottom K, Juliger S, et al. The proteasome inhibitor bortezomib acts independently of p53 and induces cell death via apoptosis and mitotic catastrophe in B-cell lymphoma cell lines. Cancer Res 2007; 67(6): 2783–2790.
- 53 Gatto S, Scappini B, Pham L, et al. The proteasome inhibitor PS-341 inhibits growth and induces apoptosis in Bcr/Abl-positive cell lines sensitive and resistant to imatinib mesylate. Haematologica 2003; 88(8): 853–863.
- 54 Vinitsky A, Michaud C, Powers JC, Orlowski M. Inhibition of the chymotrypsin-like activity of the pituitary multicatalytic proteinase complex. Biochemistry 1992; 31(39): 9421–9428.
- 55 Snider BJ, Tee LY, Canzoniero LM, Babcock DJ, Choi DW. NMDA antagonists exacerbate neuronal death caused by proteasome inhibition in cultured cortical and striatal neurons. Eur J Neurosci 2002; 15(3): 419–428.
- 56 Crawford LJ, Walker B, Ovaa H, et al. Comparative selectivity and specificity of the proteasome inhibitors BzLLLCOCHO, PS-341, and MG-132. Cancer Res 2006; 66(12): 6379–6386.
- 57 Lynas JF, Harriott P, Healy A, McKervey MA, Walker B. Inhibitors of the chymotrypsin-like activity of proteasome based on di- and tri-peptidyl alpha-keto aldehydes (glyoxals). Bioorg Med Chem Lett 1998; 8(4): 373–378.
- 58 Shah SA, Potter MW, McDade TP, et al. 26S proteasome inhibition induces apoptosis and limits growth of human pancreatic cancer. J Cell Biochem 2001; 82(1): 110–122.
- 59 Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005; 352(24): 2487–2498.
- 60 Oakervee HE, Popat R, Curry N, et al. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol 2005; 129(6): 755–762.
- 61 Orlowski RZ, Voorhees PM, Garcia RA, et al. Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies. Blood 2005; 105(8): 3058–3065.
- 62 Yang HH, Vescio R, Schenkein D, Berenson JR. A prospective, open-label safety and efficacy study of combination treatment with bortezomib (PS-341, Velcade) and melphalan in patients with relapsed or refractory multiple myeloma. Clin Lymphoma 2003; 4(2): 119–122.
- 63 Palumbo A, Avonto I, Bruno B, et al. Intermediate-dose melphalan (100 mg/m2)/bortezomib/thalidomide/dexamethasone and stem cell support in patients with refractory or relapsed myeloma. Clin Lymphoma Myeloma 2006; 6(6): 475–477.
- 64 Mateos MV, Hernandez JM, Hernandez MT, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood 2006; 108(7): 2165–2172.
- 65 Hideshima T, Richardson P, Chauhan D, et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res 2001; 61(7): 3071–3076.
- 66 Mitsiades N, Mitsiades CS, Richardson PG, et al. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications. Blood 2003; 101(6): 2377–2380.
- 67 David E, Sun SY, Waller EK, Chen J, Khuri FR, Lonial S. The combination of the farnesyl transferase inhibitor lonafarnib and the proteasome inhibitor bortezomib induces synergistic apoptosis in human myeloma cells that is associated with down-regulation of p-AKT. Blood 2005; 106(13): 4322–4329.
- 68 Chauhan D, Catley L, Li G, et al. A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from bortezomib. Cancer Cell 2005; 8(5): 407–419.
- 69 Miller CP, Ban K, Dujka ME, et al. NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells. Blood 2007; 110(1): 267–277.
- 70 Servida F, Soligo D, Delia D, et al. Sensitivity of human multiple myelomas and myeloid leukemias to the proteasome inhibitor I. Leukemia 2005; 19(12): 2324–2331.
- 71 Stapnes C, Doskeland AP, Hatfield K, et al. The proteasome inhibitors bortezomib and PR-171 have antiproliferative and proapoptotic effects on primary human acute myeloid leukaemia cells. Br J Haematol 2007; 136(6): 814–828.
- 72
Pigneux A,
Mahon FX,
Moreau-Gaudry F, et al.
Proteasome inhibition specifically sensitizes leukemic cells to anthracyclin-induced apoptosis through the accumulation of Bim and Bax pro-apoptotic proteins.
Cancer Biol Ther
2007;
6 4.
10.4161/cbt.6.4.4226 Google Scholar
- 73 Kumatori A, Tanaka K, Inamura N, et al. Abnormally high expression of proteasomes in human leukemic cells. Proc Natl Acad Sci USA 1990; 87(18): 7071–7075.
- 74 Horton TM, Pati D, Plon SE, et al. A phase 1 study of the proteasome inhibitor bortezomib in pediatric patients with refractory leukemia: a Children's Oncology Group study. Clin Cancer Res 2007; 13(5): 1516–1522.
- 75 Horton TM, Gannavarapu A, Blaney SM, D'Argenio DZ, Plon SE, Berg SL. Bortezomib interactions with chemotherapy agents in acute leukemia in vitro. Cancer Chemother Pharmacol 2006; 58(1): 13–23.
- 76 Riccioni R, Senese M, Diverio D, et al. M4 and M5 acute myeloid leukaemias display a high sensitivity to bortezomib-mediated apoptosis. Br J Haematol 2007; 139(2): 194–205.
- 77 Minderman H, Zhou Y, O'Loughlin KL, Baer MR. Bortezomib activity and in vitro interactions with anthracyclines and cytarabine in acute myeloid leukemia cells are independent of multidrug resistance mechanisms and p53 status. Cancer Chemother Pharmacol 2007; 60(2): 245–255.
- 78 Richardson PG, Hideshima T, Mitsiades C, Anderson K. Proteasome inhibition in hematologic malignancies. Ann Med 2004; 36(4): 304–314.
- 79 Yu C, Rahmani M, Conrad D, Subler M, Dent P, Grant S. The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/Abl+ cells sensitive and resistant to S TI571. Blood 2003; 102(10): 3765–3774.
- 80 Sutheesophon K, Kobayashi Y, Takatoku MA, et al. Histone deacetylase inhibitor depsipeptide (FK228) induces apoptosis in leukemic cells by facilitating mitochondrial translocation of Bax, which is enhanced by the proteasome inhibitor bortezomib. Acta Haematol 2006; 115(1–2): 78–90.
- 81 Lancet JE, Gojo I, Gotlib J, et al. A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia. Blood 2007; 109(4): 1387–1394.
- 82 Shtivelman E, Lifshitz B, Gale RP, Canaani E. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 1985; 315(6020): 550–554.
- 83 Eaves CJ, Eaves AC. Stem cell kinetics. Baillieres Clin Haematol 1997; 10(2): 233–257.
- 84 Goldman JM, Melo JV. Chronic myeloid leukaemia—advances in biology and new approaches to treatment. N Engl J Med 2003; 349(15): 1451–1464.
- 85 Mughal T, Cortes J, Cross NC, et al. Chronic myeloid leukaemia—some topical issues. Leukemia 2007; 21(7): 1347–1352.
- 86 Graham SM, Jorgensen HG, Allan E, et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 2002; 99(1): 319–325.
- 87 Elrick LJ, Jorgensen HG, Mountford JC, Holyoake TL. Punish the parent not the progeny. Blood 2005; 105(5): 1862–1866.
- 88 Copland M, Hamilton A, Elrick LJ, et al. Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 2006; 107(11): 4532–4539.
- 89 Jorgensen HG, Allan EK, Graham SM, et al. Lonafarnib reduces the resistance of primitive quiescent CML cells to imatinib mesylate in vitro. Leukemia 2005; 19(7): 1184–1191.
- 90 Jorgensen HG, Allan EK, Mountford JC, et al. Enhanced CML stem cell elimination in vitro by bryostatin priming with imatinib mesylate. Exp Hematol 2005; 33(10): 1140–1146.
- 91 Jorgensen HG, Copland M, Allan EK, et al. Intermittent exposure of primitive quiescent chronic myeloid leukemia cells to granulocyte-colony stimulating factor in vitro promotes their elimination by imatinib mesylate. Clin Cancer Res 2006; 12(2): 626–633.
- 92 Heaney NB, Holyoake TL. Therapeutic targets in chronic myeloid leukaemia. Hematol Oncol 2007; 25(2): 66–75.
- 93 Soligo D, Servida F, Delia D, et al. The apoptogenic response of human myeloid leukaemia cell lines and of normal and malignant haematopoietic progenitor cells to the proteasome inhibitor PSI. Br J Haematol 2001; 113(1): 126–135.
- 94 Yan H, Wang YC, Li D, et al. Arsenic trioxide and proteasome inhibitor bortezomib synergistically induce apoptosis in leukemic cells: the role of protein kinase Cdelta. Leukemia 2007; 21(7): 1488–1495.
- 95 Dai Y, Rahmani M, Pei XY, Dent P, Grant S. Bortezomib and flavopiridol interact synergistically to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate through both Bcr/Abl-dependent and -independent mechanisms. Blood 2004; 104(2): 509–518.
- 96 Kraus M, Ruckrich T, Reich M, et al. Activity patterns of proteasome subunits reflect bortezomib sensitivity of hematologic malignancies and are variable in primary human leukemia cells. Leukemia 2007; 21(1): 84–92.
- 97 Cusack JC Jr, Liu R, Houston M, et al. Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cancer Res 2001; 61(9): 3535–3540.
- 98 Lenz HJ. Clinical update: proteasome inhibitors in solid tumors. Cancer Treat Rev 2003; 29 (Suppl 1): 41–48.
- 99 Panwalkar A, Verstovsek S, Giles F. Nuclear factor-kappaB modulation as a therapeutic approach in hematologic malignancies. Cancer 2004; 100(8): 1578–1589.
- 100 Braun T, Carvalho G, Fabre C, Grosjean J, Fenaux P, Kroemer G. Targeting NF-kappaB in hematologic malignancies. Cell Death Differ 2006; 13(5): 748–758.
- 101 Mani A, Gelmann EP. The ubiquitin-proteasome pathway and its role in cancer. J Clin Oncol 2005; 23(21): 4776–4789.
- 102 Hideshima T, Mitsiades C, Akiyama M, et al. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood 2003; 101(4): 1530–1534.
- 103 Hideshima T, Mitsiades C, Akiyama M, et al. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood 2003; 101(4): 1530–1534.
- 104 Yu C, Friday BB, Lai JP, et al. Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways. Mol Cancer Ther 2006; 5(9): 2378–2387.
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