The Syk kinase as a therapeutic target in leukemia and lymphoma

Bibliography

• Pierce SK, Liu W. The tipping points in the initiation of B cell signalling: how small changes make big differences. Nat Rev Immunol 2010;10:767-77
   PubMed Web of Science ®Google Scholar
• Niiro H, Clark EA. Regulation of B-cell fate by antigen-receptor signals. Nat Rev Immunol 2002;2:945-56
   PubMed Web of Science ®Google Scholar
• Monroe JG. ITAM-mediated tonic signalling through pre-BCR and BCR complexes. Nat Rev Immunol 2006;6:283-94
   PubMed Web of Science ®Google Scholar
• Mocsai A, Ruland J, Tybulewicz VL. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol 2010;10:387-402
   PubMed Web of Science ®Google Scholar
• Lam KP, Kuhn R, Rajewsky K. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 1997;90:1073-83
   PubMed Web of Science ®Google Scholar
• Kraus M, Alimzhanov MB, Rajewsky N, Rajewsky K. Survival of resting mature B lymphocytes depends on BCR signaling via the Igalpha/beta heterodimer. Cell 2004;117:787-800
   PubMed Web of Science ®Google Scholar
• Geahlen RL. Syk and pTyr'd: signaling through the B cell antigen receptor. Biochim Biophys Acta 2009;1793:1115-27
   PubMed Web of Science ®Google Scholar
• Kurosaki T, Johnson SA, Pao L, Role of the Syk autophosphorylation site and SH2 domains in B cell antigen receptor signaling. J Exp Med 1995;182:1815-23
   PubMed Web of Science ®Google Scholar
• Zhang J, Kimura T, Siraganian RP. Mutations in the activation loop tyrosines of protein tyrosine kinase Syk abrogate intracellular signaling but not kinase activity. J Immunol 1998;161:4366-74
   PubMed Web of Science ®Google Scholar
• Atwell S, Adams JM, Badger J, A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase. J Biol Chem 2004;279:55827-32
   PubMed Web of Science ®Google Scholar
• Deindl S, Kadlecek TA, Brdicka T, Structural basis for the inhibition of tyrosine kinase activity of ZAP-70. Cell 2007;129:735-49
   PubMed Web of Science ®Google Scholar
• Carsetti L, Laurenti L, Gobessi S, Phosphorylation of the activation loop tyrosines is required for sustained Syk signaling and growth factor-independent B-cell proliferation. Cell Signal 2009;21:1187-94
   PubMed Web of Science ®Google Scholar
• Kitaura Y, Jang IK, Wang Y, Control of the B cell-intrinsic tolerance programs by ubiquitin ligases Cbl and Cbl-b. Immunity 2007;26:567-78
   PubMed Web of Science ®Google Scholar
• Dierks C, Adrian F, Fisch P, The ITK–SYK fusion oncogene induces a T-cell lymphoproliferative disease in mice mimicking human disease. Cancer Res 2010;70:6193-204
   PubMed Web of Science ®Google Scholar
• Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell 2007;129:1261-74
   PubMed Web of Science ®Google Scholar
• Ingley E. Src family kinases: regulation of their activities, levels and identification of new pathways. Biochim Biophys Acta 2008;1784:56-65
   PubMed Web of Science ®Google Scholar
• Young RM, Hardy IR, Clarke RL, Mouse models of non-Hodgkins lymphoma reveal Syk as an important therapeutic target. Blood 2009;113:2508-16
   PubMed Web of Science ®Google Scholar
• Delgado P, Cubelos B, Calleja E, Essential function for the GTPase TC21 in homeostatic antigen receptor signaling. Nat Immunol 2009;10:880-8
   PubMed Web of Science ®Google Scholar
• Srinivasan L, Sasaki Y, Calado DP, PI3 kinase signals BCR-dependent mature B cell survival. Cell 2009;139:573-86
   PubMed Web of Science ®Google Scholar
• Pogue SL, Kurosaki T, Bolen J, Herbst R. B cell antigen receptor-induced activation of Akt promotes B cell survival and is dependent on Syk kinase. J Immunol 2000;165:1300-6
   PubMed Web of Science ®Google Scholar
• Longo PG, Laurenti L, Gobessi S, The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells. Blood 2008;111:846-55
   PubMed Web of Science ®Google Scholar
• Kuppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer 2005;5:251-62
   PubMed Web of Science ®Google Scholar
• Chiorazzi N, Ferrarini M. B cell chronic lymphocytic leukemia: lessons learned from studies of the B cell antigen receptor. Annu Rev Immunol 2003;21:841-94
   PubMed Web of Science ®Google Scholar
• Stevenson FK, Caligaris-Cappio F. Chronic lymphocytic leukemia: revelations from the B-cell receptor. Blood 2004;103:4389-95
   PubMed Web of Science ®Google Scholar
• Messmer BT, Albesiano E, Efremov DG, Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia. J Exp Med 2004;200:519-25
   PubMed Web of Science ®Google Scholar
• Tobin G, Thunberg U, Karlsson K, Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia. Blood 2004;104:2879-85
   PubMed Web of Science ®Google Scholar
• Widhopf GF II, Rassenti LZ, Toy TL, Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins. Blood 2004;104:2499-504
   PubMed Web of Science ®Google Scholar
• Stamatopoulos K, Belessi C, Moreno C, Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: pathogenetic implications and clinical correlations. Blood 2007;109:259-70
   PubMed Web of Science ®Google Scholar
• Borche L, Lim A, Binet JL, Dighiero G. Evidence that chronic lymphocytic leukemia B lymphocytes are frequently committed to production of natural autoantibodies. Blood 1990;76:562-9
   PubMed Web of Science ®Google Scholar
• Lanemo Myhrinder A, Hellqvist E, Sidorova E, A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies. Blood 2008;111:3838-48
   PubMed Web of Science ®Google Scholar
• Chu CC, Catera R, Hatzi K, Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize non-muscle myosin heavy chain IIA. Blood 2008;112:5122-9
   PubMed Web of Science ®Google Scholar
• Chu CC, Catera R, Zhang L, Many chronic lymphocytic leukemia antibodies recognize apoptotic cells with exposed nonmuscle myosin heavy chain IIA: implications for patient outcome and cell of origin. Blood 2010;115:3907-15
   PubMed Web of Science ®Google Scholar
• Damle RN, Ghiotto F, Valetto A, B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. Blood 2002;99:4087-93
   PubMed Web of Science ®Google Scholar
• Rosenwald A, Alizadeh AA, Widhopf G, Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 2001;194:1639-47
   PubMed Web of Science ®Google Scholar
• Damle RN, Wasil T, Fais F, Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999;94:1840-7
   PubMed Web of Science ®Google Scholar
• Hamblin TJ, Davis Z, Gardiner A, Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999;94:1848-54
   PubMed Web of Science ®Google Scholar
• Crespo M, Bosch F, Villamor N, ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003;348:1764-75
   PubMed Web of Science ®Google Scholar
• Rassenti LZ, Huynh L, Toy TL, ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med 2004;351:893-901
   PubMed Web of Science ®Google Scholar
• Lanham S, Hamblin T, Oscier D, Differential signaling via surface IgM is associated with VH gene mutational status and CD38 expression in chronic lymphocytic leukemia. Blood 2003;101:1087-93
   PubMed Web of Science ®Google Scholar
• Chen L, Widhopf G, Huynh L, Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia. Blood 2002;100:4609-14
   PubMed Web of Science ®Google Scholar
• Gobessi S, Laurenti L, Longo PG, ZAP-70 enhances B-cell receptor signaling in spite of absent or inefficient tyrosine kinase activation in chronic lymphocytic leukemia and lymphoma B-cells. Blood 2007;109:2032-9
   PubMed Web of Science ®Google Scholar
• Ian Mockridge C, Potter KN, Wheatley I, Reversible anergy of sIgM-mediated signaling in the two subsets of CLL defined by VH-gene mutational status. Blood 2007;109:4424-31
   PubMed Web of Science ®Google Scholar
• Bende RJ, Aarts WM, Riedl RG, Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity. J Exp Med 2005;201:1229-41
   PubMed Web of Science ®Google Scholar
• Ivanovski M, Silvestri F, Pozzato G, Somatic hypermutation, clonal diversity, and preferential expression of the VH 51p1/VL kv325 immunoglobulin gene combination in hepatitis C virus-associated immunocytomas. Blood 1998;91:2433-42
   PubMed Web of Science ®Google Scholar
• Ferreri AJ, Guidoboni M, Ponzoni M, Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 2004;96:586-94
   PubMed Web of Science ®Google Scholar
• Goodlad JR, Davidson MM, Hollowood K, Primary cutaneous B-cell lymphoma and Borrelia burgdorferi infection in patients from the Highlands of Scotland. Am J Surg Pathol 2000;24:1279-85
   PubMed Web of Science ®Google Scholar
• Wotherspoon AC, Doglioni C, Diss TC, Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 1993;342:575-7
   PubMed Web of Science ®Google Scholar
• Mazzaro C, Franzin F, Tulissi P, Regression of monoclonal B-cell expansion in patients affected by mixed cryoglobulinemia responsive to alpha-interferon therapy. Cancer 1996;77:2604-13
   PubMed Web of Science ®Google Scholar
• Hermine O, Lefrere F, Bronowicki JP, Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 2002;347:89-94
   PubMed Web of Science ®Google Scholar
• Ferreri AJ, Ponzoni M, Guidoboni M, Regression of ocular adnexal lymphoma after Chlamydia psittaci-eradicating antibiotic therapy. J Clin Oncol 2005;23:5067-73
   PubMed Web of Science ®Google Scholar
• Guillaume N, Alleaume C, Munfus D, ZAP-70 tyrosine kinase is constitutively expressed and phosphorylated in B-lineage acute lymphoblastic leukemia cells. Haematologica 2005;90:899-905
   PubMed Web of Science ®Google Scholar
• Leseux L, Hamdi SM, Al Saati T, Syk-dependent mTOR activation in follicular lymphoma cells. Blood 2006;108:4156-62
   PubMed Web of Science ®Google Scholar
• Gururajan M, Jennings CD, Bondada S. Cutting edge: constitutive B cell receptor signaling is critical for basal growth of B lymphoma. J Immunol 2006;176:5715-19
   PubMed Web of Science ®Google Scholar
• Chen L, Monti S, Juszczynski P, SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood 2008;111:2230-7
   PubMed Web of Science ®Google Scholar
• Rinaldi A, Kwee I, Taborelli M, Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma. Br J Haematol 2006;132:303-16
   PubMed Web of Science ®Google Scholar
• Gobessi S, Laurenti L, Longo PG, Inhibition of constitutive and BCR-induced Syk activation downregulates Mcl-1 and induces apoptosis in chronic lymphocytic leukemia B cells. Leukemia 2009;23:686-97
   PubMed Web of Science ®Google Scholar
• Quiroga MP, Balakrishnan K, Kurtova AV, B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406. Blood 2009;114:1029-37
   PubMed Web of Science ®Google Scholar
• Buchner M, Fuchs S, Prinz G, Spleen tyrosine kinase is overexpressed and represents a potential therapeutic target in chronic lymphocytic leukemia. Cancer Res 2009;69:5424-32
   PubMed Web of Science ®Google Scholar
• Baudot AD, Jeandel PY, Mouska X, The tyrosine kinase Syk regulates the survival of chronic lymphocytic leukemia B cells through PKCdelta and proteasome-dependent regulation of Mcl-1 expression. Oncogene 2009;28:3261-73
   PubMed Web of Science ®Google Scholar
• Gururajan M, Dasu T, Shahidain S, Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth. J Immunol 2007;178:111-21
   PubMed Web of Science ®Google Scholar
• Wossning T, Herzog S, Kohler F, Deregulated Syk inhibits differentiation and induces growth factor-independent proliferation of pre-B cells. J Exp Med 2006;203:2829-40
   PubMed Web of Science ®Google Scholar
• Coffey G, Luan P, Delaney S, Specific inhibition of Syk is sufficient to disrupt proliferation and survival of non-Hodgkin's lymphoma cell lines without concomitant inhibition of JAK. ASH Annual Meeting Abstracts. Blood 2008;112:1794
   PubMed Web of Science ®Google Scholar
• Uckun FM, Qazi S, Ma H, STAT3 is a substrate of SYK tyrosine kinase in B-lineage leukemia/lymphoma cells exposed to oxidative stress. Proc Natl Acad Sci USA 2010;107:2902-7
   PubMed Web of Science ®Google Scholar
• Uckun FM, Ek RO, Jan ST, Targeting SYK kinase-dependent anti-apoptotic resistance pathway in B-lineage acute lymphoblastic leukaemia (ALL) cells with a potent SYK inhibitory pentapeptide mimic. Br J Haematol 2010;149:508-17
   PubMed Web of Science ®Google Scholar
• Song Z, Lu P, Furman RR, Activities of SYK and PLCgamma2 predict apoptotic response of CLL cells to SRC tyrosine kinase inhibitor dasatinib. Clin Cancer Res 2010;16:587-99
   PubMed Web of Science ®Google Scholar
• Davis RE, Ngo VN, Lenz G, Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 2010;463:88-92
   PubMed Web of Science ®Google Scholar
• Uckun FM, Qazi S. Spleen tyrosine kinase as a molecular target for treatment of leukemias and lymphomas. Expert Rev Anticancer Ther 2010;10:1407-18
   PubMed Web of Science ®Google Scholar
• Alizadeh AA, Eisen MB, Davis RE, Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000;403:503-11
   PubMed Web of Science ®Google Scholar
• Chen L, Juszczynski P, Takeyama K, Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation. Blood 2006;108:3428-33
   PubMed Web of Science ®Google Scholar
• Motiwala T, Majumder S, Kutay H, Methylation and silencing of protein tyrosine phosphatase receptor type O in chronic lymphocytic leukemia. Clin Cancer Res 2007;13:3174-81
   Google Scholar
• Juszczynski P, Chen L, O'Donnell E, BCL6 modulates tonic BCR signaling in diffuse large B-cell lymphomas by repressing the SYK phosphatase, PTPROt. Blood 2009;114:5315-21
   PubMed Web of Science ®Google Scholar
• Motiwala T, Datta J, Kutay H, Lyn kinase and ZAP70 are substrates of PTPROt in B-cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF-R inhibitor pazopanib. J Cell Biochem 2010;110:846-56
   PubMed Web of Science ®Google Scholar
• Radcliffe CM, Arnold JN, Suter DM, Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor. J Biol Chem 2007;282:7405-15
   PubMed Web of Science ®Google Scholar
• Coelho V, Krysov S, Ghaemmaghami AM, Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins. Proc Natl Acad Sci USA 2010;107:18587-92
   PubMed Web of Science ®Google Scholar
• Kuno Y, Abe A, Emi N, Constitutive kinase activation of the TEL–Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12). Blood 2001;97:1050-5
   PubMed Web of Science ®Google Scholar
• Kanie T, Abe A, Matsuda T, TEL–Syk fusion constitutively activates PI3-K/Akt, MAPK and JAK2-independent STAT5 signal pathways. Leukemia 2004;18:548-55
   PubMed Web of Science ®Google Scholar
• Streubel B, Vinatzer U, Willheim M, Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma. Leukemia 2006;20:313-18
   PubMed Web of Science ®Google Scholar
• Pechloff K, Holch J, Ferch U, The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma. J Exp Med 2010;207:1031-44
   PubMed Web of Science ®Google Scholar
• Feldman AL, Sun DX, Law ME, Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas. Leukemia 2008;22:1139-43
   PubMed Web of Science ®Google Scholar
• Wilcox RA, Sun DX, Novak A, Inhibition of Syk protein tyrosine kinase induces apoptosis and blocks proliferation in T-cell non-Hodgkin's lymphoma cell lines. Leukemia 2010;24:229-32
   PubMed Web of Science ®Google Scholar
• Hahn CK, Berchuck JE, Ross KN, Proteomic and genetic approaches identify Syk as an AML target. Cancer Cell 2009;16:281-94
   PubMed Web of Science ®Google Scholar
• Refaeli Y, Field KA, Turner BC, The protooncogene MYC can break B-cell tolerance. Proc Natl Acad Sci USA 2005;102:4097-102
   PubMed Web of Science ®Google Scholar
• Suljagic M, Longo PG, Bennardo S, The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the E{micro}- TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling. Blood 2010;116:4894-905
   PubMed Web of Science ®Google Scholar
• Yan XJ, Albesiano E, Zanesi N, B cell receptors in TCL1 transgenic mice resemble those of aggressive, treatment-resistant human chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2006;103:11713-18
   PubMed Web of Science ®Google Scholar
• Braselmann S, Taylor V, Zhao H, R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther 2006;319:998-1008
   PubMed Web of Science ®Google Scholar
• Podolanczuk A, Lazarus AH, Crow AR, Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk. Blood 2009;113:3154-60
   PubMed Web of Science ®Google Scholar
• Turner M, Mee PJ, Costello PS, Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 1995;378:298-302
   PubMed Web of Science ®Google Scholar
• Moore WJ, Richard D, Thorarensen A. An analysis of the diaminopyrimidine patent estates describing spleen tyrosine kinase inhibitors by Rigel and Portola. Expert Opin Ther Pat 2010;20:1703-22
   PubMed Web of Science ®Google Scholar
• Weinblatt ME, Kavanaugh A, Burgos-Vargas R, Treatment of rheumatoid arthritis with a Syk kinase inhibitor: a twelve-week, randomized, placebo-controlled trial. Arthritis Rheum 2008;58:3309-18
   PubMed Web of Science ®Google Scholar
• Weinblatt ME, Kavanaugh A, Genovese MC, An oral spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis. N Engl J Med 2010;363:1303-12
   PubMed Web of Science ®Google Scholar
• Genovese MC, Kavanaugh A, Weinblatt ME, An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: a three-month randomized, placebo-controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents. Arthritis Rheum 2011;63:337-45
   PubMed Web of Science ®Google Scholar
• Friedberg JW, Sharman J, Sweetenham J, Inhibition of Syk with fostamatinib disodium has significant clinical activity in non Hodgkin's lymphoma and chronic lymphocytic leukemia. Blood 2010;115:2578-85
   PubMed Web of Science ®Google Scholar
• Zent CS, LaPlant BR, Johnston PB, The treatment of recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) with everolimus results in clinical responses and mobilization of CLL cells into the circulation. Cancer 2010;116:2201-7
   PubMed Web of Science ®Google Scholar
• Herishanu Y, Perez-Galan P, Liu D, The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood 2011;117:563-74
   PubMed Web of Science ®Google Scholar
• Buchner M, Baer C, Prinz G, Spleen tyrosine kinase inhibition prevents chemokine- and integrin-mediated stromal protective effects in chronic lymphocytic leukemia. Blood 2010;115:4497-506
   PubMed Web of Science ®Google Scholar
• Burger JA, O'Brien S, Fowler N, The Bruton's tyrosine kinase inhibitor, PCI-32765, is well tolerated and demonstrates promising clinical activity in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL): an update on ongoing phase 1 studies. ASH Annual Meeting Abstracts. Blood 2010;116:57
   Web of Science ®Google Scholar
• Furman RR, Byrd JC, Brown JR, CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3dkinase (PIK3) delta, demonstrates clinical activity and pharmacodynamic effects in patients with relapsed or refractory chronic lymphocytic leukemia. ASH Annual Meeting Abstracts. Blood 2010;116:55
   Google Scholar
• Petlickovski A, Laurenti L, Li X, Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B-cells. Blood 2005;105:4820-7
   PubMed Web of Science ®Google Scholar
• Uckun FM, Dibirdik I, Qazi S. Augmentation of the antileukemia potency of total-body irradiation (TBI) by a novel P-site inhibitor of spleen tyrosine kinase (SYK). Radiat Res 2010;174:526-31
   PubMed Web of Science ®Google Scholar
• Moreton P, Hillmen P. Alemtuzumab therapy in B-cell lymphoproliferative disorders. Semin Oncol 2003;30:493-501
   PubMed Web of Science ®Google Scholar