500
Views
23
CrossRef citations to date
0
Altmetric
Reviews

JAK2 inhibition for the treatment of hematologic and solid malignancies

, BS, , MD & , MD PhD
Pages 637-655 | Published online: 12 Apr 2012

Bibliography

  • Baxter EJ, Scott LM, Campbell PJ, Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:1054-61
  • James C, Ugo V, Le Couedic JP, A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005;434:1144-8
  • Kralovics R, Passamonti F, Buser AS, A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005;352:1779-90
  • Levine RL, Wadleigh M, Cools J, Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005;7:387-97
  • Vainchenker W, Dusa A, Constantinescu SN. JAKs in pathology: role of janus kinases in hematopoietic malignancies and immunodeficiencies. Semin Cell Dev Biol 2008;19:385-93
  • Rane SG, Reddy EP. Janus kinases: components of multiple signaling pathways. Oncogene 2000;19:5662-79
  • Quintas-Cardama A, Kantarjian H, Cortes J, Janus kinase inhibitors for the treatment of myeloproliferative neoplasias and beyond. Nat Rev Drug Discov 2011;10:127-40
  • Levy DE, Lee CK. What does stat3 do? J Clin Invest 2002;109:1143-8
  • Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for stat3. Nat Rev Cancer 2009;9:798-809
  • Croker BA, Kiu H, Nicholson SE. SOCS regulation of the JAK/STAT signalling pathway. Semin Cell Dev Biol 2008;19:414-22
  • Valentino L, Pierre J. JAK/STAT signal transduction: regulators and implication in hematological malignancies. Biochem Pharmacol 2006;71:713-21
  • Ungureanu D, Wu J, Pekkala T, The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Nat Struct Mol Biol 2011;18:971-6
  • Sayyah J, Sayeski PP. Jak2 inhibitors: rationale and role as therapeutic agents in hematologic malignancies. Curr Oncol Rep 2009;11:117-24
  • Peeters P, Raynaud SD, Cools J, Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood 1997;90:2535-40
  • Lacronique V, Boureux A, Valle VD, A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science 1997;278:1309-12
  • Ho JM, Beattie BK, Squire JA, Fusion of the ets transcription factor TEL to Jak2 results in constitutive Jak-Stat signaling. Blood 1999;93:4354-64
  • Griesinger F, Hennig H, Hillmer F, A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemia. Genes Chromosomes Cancer 2005;44:329-33
  • Cirmena G, Aliano S, Fugazza G, A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11) in a patient with acute myeloid leukemia. Cancer Genet Cytogenet 2008;183:105-8
  • Murati A, Gelsi-Boyer V, Adelaide J, PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation. Leukemia 2005;19:1692-6
  • Bousquet M, Quelen C, De Mas V, The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene. Oncogene 2005;24:7248-52
  • Adelaide J, Perot C, Gelsi-Boyer V, A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma. Leukemia 2006;20:536-7
  • Reiter A, Walz C, Watmore A, The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. Cancer Res 2005;65:2662-7
  • Hoeller S, Walz C, Reiter A, PCM1-JAK2-fusion: a potential treatment target in myelodysplastic-myeloproliferative and other hemato-lymphoid neoplasms. Expert Opin Ther Targets 2011;15:53-62
  • Van Roosbroeck K, Cox L, Tousseyn T, JAK2 rearrangements, including the novel SEC31A-JAK2 fusion, are recurrent in classical Hodgkin lymphoma. Blood 2011;117:4056-64
  • Poitras JL, Dal Cin P, Aster JC, Novel SSBP2-JAK2 fusion gene resulting from a t(5;9)(q14.1;p24.1) in pre-B acute lymphocytic leukemia. Genes Chromosomes Cancer 2008;47:884-9
  • Najfeld V, Cozza A, Berkofsy-Fessler W, Numerical gain and structural rearrangements of JAK2, identified by FISH, characterize both JAK2617V > F-positive and -negative patients with Ph-negative MPD, myelodysplasia, and B-lymphoid neoplasms. Exp Hematol 2007;35:1668-76
  • Perez B, Kosmider O, Cassinat B, Genetic typing of CBL, ASXL1, RUNX1, TET2 and JAK2 in juvenile myelomonocytic leukaemia reveals a genetic profile distinct from chronic myelomonocytic leukaemia. Br J Haematol 2010;151:460-8
  • Tono C, Xu G, Toki T, JAK2 Val617Phe activating tyrosine kinase mutation in juvenile myelomonocytic leukemia. Leukemia 2005;19:1843-4
  • Zecca M, Bergamaschi G, Kratz C, JAK2 V617F mutation is a rare event in juvenile myelomonocytic leukemia. Leukemia 2007;21:367-9
  • Jelinek J, Oki Y, Gharibyan V, JAK2 mutation 1849G > T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. Blood 2005;106:3370-3
  • Holtan SG, Hoyer JD, Buadi FK. Multiple myeloma with concomitant JAK2-positive essential thrombocythemia post-successful autologous peripheral blood hematopoietic stem cell transplant. Bone Marrow Transplant 2011;46:615
  • Lee JW, Kim YG, Soung YH, The JAK2 V617F mutation in de novo acute myelogenous leukemias. Oncogene 2006;25:1434-6
  • Fiorini A, Farina G, Reddiconto G, Screening of JAK2 V617F mutation in multiple myeloma. Leukemia 2006;20:1912-13
  • Melzner I, Weniger MA, Menz CK, Absence of the JAK2 V617F activating mutation in classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma. Leukemia 2006;20:157-8
  • Lee JW, Soung YH, Kim SY, JAK2 V617F mutation is uncommon in non-Hodgkin lymphomas. Leuk Lymphoma 2006;47:313-14
  • Sulong S, Case M, Minto L, The V617F mutation in Jak2 is not found in childhood acute lymphoblastic leukaemia. Br J Haematol 2005;130:964-5
  • Kratz CP, Boll S, Kontny U, Mutational screen reveals a novel JAK2 mutation, L611S, in a child with acute lymphoblastic leukemia. Leukemia 2006;20:381-3
  • Malinge S, Ben-Abdelali R, Settegrana C, Novel activating JAK2 mutation in a patient with down syndrome and B-cell precursor acute lymphoblastic leukemia. Blood 2007;109:2202-4
  • Bercovich D, Ganmore I, Scott LM, Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome. Lancet 2008;372:1484-92
  • Gaikwad A, Rye CL, Devidas M, Prevalence and clinical correlates of JAK2 mutations in down syndrome acute lymphoblastic leukaemia. Br J Haematol 2009;144:930-2
  • Scott LM, Tong W, Levine RL, JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007;356:459-68
  • Scott LM. The JAK2 exon 12 mutations: a comprehensive review. Am J Hematol 2011;86:668-76
  • Mercher T, Wernig G, Moore SA, JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model. Blood 2006;108:2770-9
  • Joos S, Kupper M, Ohl S, Genomic imbalances including amplification of the tyrosine kinase gene JAK2 in CD30+ Hodgkin cells. Cancer Res 2000;60:549-52
  • Green MR, Monti S, Rodig SJ, Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood 2010;116:3268-77
  • Meier C, Hoeller S, Bourgau C, Recurrent numerical aberrations of JAK2 and deregulation of the JAK2-STAT cascade in lymphomas. Mod Pathol 2009;22:476-87
  • Mottok A, Renne C, Willenbrock K, Somatic hypermutation of SOCS1 in lymphocyte-predominant Hodgkin lymphoma is accompanied by high JAK2 expression and activation of STAT6. Blood 2007;110:3387-90
  • Melzner I, Bucur AJ, Bruderlein S, Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2 action in the MedB-1 mediastinal lymphoma line. Blood 2005;105:2535-42
  • Ikezoe T, Kojima S, Furihata M, Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia. Int J Cancer 2011;129:2512-21
  • Yang J, Ikezoe T, Nishioka C, AZ960, a novel Jak2 inhibitor, induces growth arrest and apoptosis in adult T-cell leukemia cells. Mol Cancer Ther 2010;9:3386-95
  • Lee JW, Soung YH, Kim SY, Absence of JAK2 V617F mutation in gastric cancers. Acta Oncol 2006;45:222-3
  • Herreros-Villanueva M, Garcia-Giron C, Er TK. No evidence for JAK2 V617F mutation in colorectal cancer. Br J Biomed Sci 2010;67:220-2
  • Gu L, Zhu XH, Visakorpi T, Activating mutation (V617F) in the tyrosine kinase JAK2 is absent in locally-confined or castration-resistant prostate cancer. Anal Cell Pathol (Amst) 2010;33:55-9
  • Zhao J, Moch H. Absence of JH2 domain mutation of the tyrosine kinase JAK2 in renal cell carcinomas. Acta Oncol 2008;47:474-6
  • Scott LM, Campbell PJ, Baxter EJ, The V617F JAK2 mutation is uncommon in cancers and in myeloid malignancies other than the classic myeloproliferative disorders. Blood 2005;106:2920-1
  • Hedvat M, Huszar D, Herrmann A, The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell 2009;16:487-97
  • Liu H, Tekle C, Chen YW, B7-H3 silencing increases paclitaxel sensitivity by abrogating Jak2/Stat3 phosphorylation. Mol Cancer Ther 2011;10:960-71
  • Lakshmanan I, Ponnusamy MP, Das S, MUC16 induced rapid G2/M transition via interactions with JAK2 for increased proliferation and anti-apoptosis in breast cancer cells. Oncogene 2011;31:805-17
  • Wagner KU, Rui H. Jak2/Stat5 signaling in mammogenesis, breast cancer initiation and progression. J Mammary Gland Biol Neoplasia 2008;13:93-103
  • Acs G, Acs P, Beckwith SM, Erythropoietin and erythropoietin receptor expression in human cancer. Cancer Res 2001;61:3561-5
  • Shi Z, Hodges VM, Dunlop EA, Erythropoietin-induced activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK pathways promotes malignant cell behavior in a modified breast cancer cell line. Mol Cancer Res 2010;8:615-26
  • Liang K, Esteva FJ, Albarracin C, Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-mediated Src activation and PTEN inactivation. Cancer Cell 2010;18:423-35
  • Bohlius J, Schmidlin K, Brillant C, Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet 2009;373:1532-42
  • Tonelli M, Hemmelgarn B, Reiman T, Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis. CMAJ 2009;180:E62-71
  • Mohyeldin A, Lu H, Dalgard C, Erythropoietin signaling promotes invasiveness of human head and neck squamous cell carcinoma. Neoplasia 2005;7:537-43
  • Lai SY, Childs EE, Xi S, Erythropoietin-mediated activation of JAK-STAT signaling contributes to cellular invasion in head and neck squamous cell carcinoma. Oncogene 2005;24:4442-9
  • Lee TL, Yeh J, Van Waes C, Epigenetic modification of SOCS-1 differentially regulates STAT3 activation in response to interleukin-6 receptor and epidermal growth factor receptor signaling through JAK and/or MEK in head and neck squamous cell carcinomas. Mol Cancer Ther 2006;5:8-19
  • Kupferman ME, Jayakumar A, Zhou G, Therapeutic suppression of constitutive and inducible JAK\⊂STAT activation in head and neck squamous cell carcinoma. J Exp Ther Oncol 2009;8:117-27
  • Shim SH, Sung MW, Park SW, Absence of STAT1 disturbs the anticancer effect induced by STAT3 inhibition in head and neck carcinoma cell lines. Int J Mol Med 2009;23:805-10
  • Sen B, Saigal B, Parikh N, Sustained Src inhibition results in signal transducer and activator of transcription 3 (STAT3) activation and cancer cell survival via altered Janus-activated kinase-STAT3 binding. Cancer Res 2009;69:1958-65
  • Sen B, Peng SH, Woods DM, STAT5A-mediated SOCS2 expression regulates Jak2 and STAT3 activity following c-Src inhibition in head and neck squamous carcinoma. Clin Cancer Res 2011;18:127-39
  • Zhou J, Xie Y, Zhao Y, Human gastrin mRNA expression up-regulated by Helicobacter pylori CagA through MEK/ERK and JAK2-signaling pathways in gastric cancer cells. Gastric Cancer 2011;14:322-31
  • Ding L, Xu Y, Zhang W, MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2. Cell Res 2010;20:784-93
  • Du W, Hong J, Wang YC, Inhibition of JAK2/STAT3 signaling induces colorectal cancer cell apoptosis via mitochondrial pathway. J Cell Mol Med 2011 doi:10.1111/j.1582-4934.2011.01483.x
  • Xiong H, Du W, Zhang YJ, Trichostatin A, a histone deacetylase inhibitor, suppresses JAK2/STAT3 signaling via inducing the promoter-associated histone acetylation of SOCS1 and SOCS3 in human colorectal cancer cells. Mol Carcinog 2011;51:178-84
  • Xiong H, Chen ZF, Liang QC, Inhibition of DNA methyltransferase induces G2 cell cycle arrest and apoptosis in human colorectal cancer cells via inhibition of JAK2/STAT3/STAT5 signalling. J Cell Mol Med 2009;13:3668-79
  • Shi S, Calhoun HC, Xia F, JAK signaling globally counteracts heterochromatic gene silencing. Nat Genet 2006;38:1071-6
  • Scholz A, Heinze S, Detjen KM, Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology 2003;125:891-905
  • Corcoran RB, Contino G, Deshpande V, STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis. Cancer Res 2011;71:5020-9
  • Thoennissen NH, Iwanski GB, Doan NB, Cucurbitacin B induces apoptosis by inhibition of the JAK/STAT pathway and potentiates antiproliferative effects of gemcitabine on pancreatic cancer cells. Cancer Res 2009;69:5876-84
  • Liu Y, Liu A, Li H, Celecoxib inhibits interleukin-6/interleukin-6 receptor-induced JAK2/STAT3 phosphorylation in human hepatocellular carcinoma cells. Cancer Prev Res (Phila) 2011;4:1296-305
  • Niwa Y, Kanda H, Shikauchi Y, Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma. Oncogene 2005;24:6406-17
  • Huang WL, Yeh HH, Lin CC, Signal transducer and activator of transcription 3 activation up-regulates interleukin-6 autocrine production: a biochemical and genetic study of established cancer cell lines and clinical isolated human cancer cells. Mol Cancer 2010;9:309
  • Chang KT, Tsai CM, Chiou YC, IL-6 induces neuroendocrine dedifferentiation and cell proliferation in non-small cell lung cancer cells. Am J Physiol Lung Cell Mol Physiol 2005;289:L446-53
  • Takata S, Takigawa N, Segawa Y, STAT3 expression in activating EGFR-driven adenocarcinoma of the lung. Lung Cancer 2012;75:24-9
  • Sun Y, Moretti L, Giacalone NJ, Inhibition of JAK2 signaling by TG101209 enhances radiotherapy in lung cancer models. J Thorac Oncol 2011;6:699-706
  • Yoon YK, Kim HP, Han SW, KRAS mutant lung cancer cells are differentially responsive to MEK inhibitor due to AKT or STAT3 activation: implication for combinatorial approach. Mol Carcinog 2010;49:353-62
  • Yu H, Jove R. The STATs of cancer–new molecular targets come of age. Nat Rev Cancer 2004;4:97-105
  • Zhao M, Gao FH, Wang JY, JAK2/STAT3 signaling pathway activation mediates tumor angiogenesis by upregulation of VEGF and bFGF in non-small-cell lung cancer. Lung Cancer 2011;73:366-74
  • Italiano A, Attias R, Aurias A, Molecular cytogenetic characterization of a metastatic lung sarcomatoid carcinoma: 9p23 neocentromere and 9p23-p24 amplification including JAK2 and JMJD2C. Cancer Genet Cytogenet 2006;167:122-30
  • Murata T. Immunoprecipitation to determine JAK kinase activation in response to interleukins in ovarian cancer. Methods Mol Med 2001;39:567-70
  • Yue P, Zhang X, Paladino D, Hyperactive EGF receptor, Jaks and Stat3 signaling promote enhanced colony-forming ability, motility and migration of cisplatin-resistant ovarian cancer cells. Oncogene 2011 doi: 10.1038/onc.2011.409
  • Colomiere M, Findlay J, Ackland L, Epidermal growth factor-induced ovarian carcinoma cell migration is associated with JAK2/STAT3 signals and changes in the abundance and localization of alpha6beta1 integrin. Int J Biochem Cell Biol 2009;41:1034-45
  • Colomiere M, Ward AC, Riley C, Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial-mesenchymal transition in ovarian carcinomas. Br J Cancer 2009;100:134-44
  • Arbel R, Rojansky N, Klein BY, Inhibitors that target protein kinases for the treatment of ovarian carcinoma. Am J Obstet Gynecol 2003;188:1283-90
  • Badgwell DB, Lu Z, Le K, The tumor-suppressor gene ARHI (DIRAS3) suppresses ovarian cancer cell migration through inhibition of the Stat3 and FAK/Rho signaling pathways. Oncogene 2011;31:68-79
  • Song H, Sondak VK, Barber DL, Modulation of Janus kinase 2 by cisplatin in cancer cells. Int J Oncol 2004;24:1017-26
  • Jo M, Park MH, Kollipara PS, Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicol Appl Pharmacol 2011;258:72-81
  • McFarland BC, Ma JY, Langford CP, Therapeutic Potential of AZD1480 for the Treatment of Human Glioblastoma. Mol Cancer Ther 2011;10:2384-93
  • Senft C, Priester M, Polacin M, Inhibition of the JAK-2/STAT3 signaling pathway impedes the migratory and invasive potential of human glioblastoma cells. J Neurooncol 2011;101:393-403
  • Yang F, Brown C, Buettner R, Sorafenib induces growth arrest and apoptosis of human glioblastoma cells through the dephosphorylation of signal transducers and activators of transcription 3. Mol Cancer Ther 2010;9:953-62
  • Abdulghani J, Gu L, Dagvadorj A, Stat3 promotes metastatic progression of prostate cancer. Am J Pathol 2008;172:1717-28
  • Lucia E, Recchia AG, Gentile M, Janus kinase 2 inhibitors in myeloproliferative disorders. Expert Opin Investig Drugs 2011;20:41-59
  • Quintas-Cardama A, Verstovsek S. New JAK2 inhibitors for myeloproliferative neoplasms. Expert Opin Investig Drugs 2011;20:961-72
  • Harry BL, Jimeno A. TG-101348. Drugs Fut 2011;36:819-24
  • Verstovsek S, Kantarjian H, Mesa RA, Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010;363:1117-27
  • Tefferi A, Pardanani A. Serious adverse events during ruxolitinib treatment discontinuation in patients with myelofibrosis. Mayo Clin Proc 2011;86:1188-91
  • Tefferi A, Litzow MR, Pardanani A. Long-term outcome of treatment with ruxolitinib in myelofibrosis. N Engl J Med 2011;365:1455-7
  • Harrison C, Kiladjian JJ, Al-Ali HK, JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012;366:787-98
  • Verstovsek S, Mesa RA, Gotlib J, A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012;366:799-807
  • Pardanani A, Gotlib JR, Jamieson C, Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 2011;29:789-96
  • Lasho T, Tefferi A, Pardanani A. Inhibition of JAK-STAT signaling by TG101348: a novel mechanism for inhibition of KITD816V-dependent growth in mast cell leukemia cells. Leukemia 2010;24:1378-80
  • Pardanani A, Lasho T, Smith G, CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia 2009;23:1441-5
  • Tyner JW, Bumm TG, Deininger J, CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood 2010;115:5232-40
  • Monaghan KA, Khong T, Burns CJ, The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells. Leukemia 2011;25:1891-9
  • Stein BL, Crispino JD, Moliterno AR. Janus kinase inhibitors: an update on the progress and promise of targeted therapy in the myeloproliferative neoplasms. Curr Opin Oncol 2011;23:609-16
  • Arkenau HT, Plummer R, Molife LR, A phase I dose escalation study of AT9283, a small molecule inhibitor of aurora kinases, in patients with advanced solid malignancies. Ann Oncol 2011 doi:10.1093/annonc/mdr451
  • Qi W, Liu X, Cooke LS, AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas. Int J Cancer 2011 doi: 10.1002/ijc.26324
  • Santo L, Hideshima T, Cirstea D, Antimyeloma activity of a multitargeted kinase inhibitor, AT9283, via potent Aurora kinase and STAT3 inhibition either alone or in combination with lenalidomide. Clin Cancer Res 2011;17:3259-71
  • Tanaka R, Squires MS, Kimura S, Activity of the multitargeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL-positive leukemic cells. Blood 2010;116:2089-95
  • Curry J, Angove H, Fazal L, Aurora B kinase inhibition in mitosis: strategies for optimising the use of aurora kinase inhibitors such as AT9283. Cell Cycle 2009;8:1921-9
  • Dawson MA, Curry JE, Barber K, AT9283, a potent inhibitor of the aurora kinases and Jak2, has therapeutic potential in myeloproliferative disorders. Br J Haematol 2010;150:46-57
  • Harrington EA, Bebbington D, Moore J, VX-680, a potent and selective small-molecule inhibitor of the aurora kinases, suppresses tumor growth in vivo. Nat Med 2004;10:262-7
  • Lin YG, Immaneni A, Merritt WM, Targeting aurora kinase with MK-0457 inhibits ovarian cancer growth. Clin Cancer Res 2008;14:5437-46
  • Li Y, Zhang ZF, Chen J, VX680/MK-0457, a potent and selective aurora kinase inhibitor, targets both tumor and endothelial cells in clear cell renal cell carcinoma. Am J Transl Res 2010;2:296-308
  • Arlot-Bonnemains Y, Baldini E, Martin B, Effects of the Aurora kinase inhibitor VX-680 on anaplastic thyroid cancer-derived cell lines. Endocr Relat Cancer 2008;15:559-68
  • Huang XF, Luo SK, Xu J, Aurora kinase inhibitory VX-680 increases Bax/Bcl-2 ratio and induces apoptosis in Aurora-A-high acute myeloid leukemia. Blood 2008;111:2854-65
  • Giles FJ, Cortes J, Jones D, MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood 2007;109:500-2
  • Dai Y, Chen S, Venditti CA, Vorinostat synergistically potentiates MK-0457 lethality in chronic myelogenous leukemia cells sensitive and resistant to imatinib mesylate. Blood 2008;112:793-804
  • Okabe S, Tauchi T, Ohyashiki JH, Mechanism of MK-0457 efficacy against BCR-ABL positive leukemia cells. Biochem Biophys Res Commun 2009;380:775-9
  • Okabe S, Tauchi T, Ohyashiki K. Efficacy of MK-0457 and in combination with vorinostat against Philadelphia chromosome positive acute lymphoblastic leukemia cells. Ann Hematol 2010;89:1081-7
  • Fei F, Stoddart S, Groffen J, Activity of the Aurora kinase inhibitor VX-680 against Bcr/Abl-positive acute lymphoblastic leukemias. Mol Cancer Ther 2010;9:1318-27
  • Traynor AM, Hewitt M, Liu G, Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. Cancer Chemother Pharmacol 2011;67:305-14
  • Sanchez-Guijo FM, Lopez-Jimenez J, Gonzalez T, Multitargeted sequential therapy with MK-0457 and dasatinib followed by stem cell transplantation for T315I mutated chronic myeloid leukemia. Leuk Res 2009;33:e20-2
  • Hexner EO, Serdikoff C, Jan M, Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood 2008;111:5663-71
  • Norris RE, Minturn JE, Brodeur GM, Preclinical evaluation of lestaurtinib (CEP-701) in combination with retinoids for neuroblastoma. Cancer Chemother Pharmacol 2011;68:1469-75
  • Minturn JE, Evans AE, Villablanca JG, Phase I trial of lestaurtinib for children with refractory neuroblastoma: a new approaches to neuroblastoma therapy consortium study. Cancer Chemother Pharmacol 2011;68:1057-65
  • Iyer R, Evans AE, Qi X, Lestaurtinib enhances the antitumor efficacy of chemotherapy in murine xenograft models of neuroblastoma. Clin Cancer Res 2010;16:1478-85
  • Knapper S, Burnett AK, Littlewood T, A phase II trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood 2006;108:3262-70
  • Levis M, Ravandi F, Wang ES, Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood 2011;117:3294-301
  • Santos FP, Kantarjian HM, Jain N, Phase II study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood 2010;115:1131-6
  • Hexner E, Goldberg JD, Prchal JT, A multicenter, open label phase I/II study of CEP701 (Lestaurtinib) in adults with myelofibrosis; a report on phase I: a study of the myeloproliferative disorders research consortium (MPDRC). Blood (ASH Annual Meeting Abstracts) 2009;114: Abstract 754
  • William AD, Lee AC, Blanchard S, Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1. 1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J Med Chem 2011;54:4638-58
  • Hart S, Goh KC, Novotny-Diermayr V, SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies. Leukemia 2011;25:1751-9
  • Deeg HJ, Odenike O, Scott BL, Phase II study of SB1518, an orally available novel JAK2 inhibitor, in patients with myelofibrosis. J Clin Oncol 2011;29(Suppl):abstract 6515
  • Paquette R, Sokol L, Shah NP, A phase I study of XL019, a selective JAK2 Inhibitor, in patients with polycythemia vera. Blood (ASH Annual Meeting Abstracts) 2008;112: Abstract 971
  • Shah NP, Olszynski P, Sokol L, A phase I study of XL019, a selective JAK2 inhibitor, in patients with Primary Myelofibrosis, Post-Polycythemia Vera, or post-essential thrombocythemia myelofibrosis. Blood (ASH Annual Meeting Abstracts) 2008;112: Abstract 98)
  • Scuto A, Krejci P, Popplewell L, The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival. Leukemia 2011;25:538-50
  • Xin H, Herrmann A, Reckamp K, Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480. Cancer Res 2011;71:6601-10
  • Purandare AV, McDevitt TM, Wan H, Characterization of BMS-911543, a functionally selective small-molecule inhibitor of JAK2. Leukemia 2011;26:280-288
  • Guerini V, Barbui V, Spinelli O, The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2(V617F). Leukemia 2008;22:740-7
  • Hertzberg L, Vendramini E, Ganmore I, Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. Blood 2010;115:1006-17
  • Andrikovics H, Nahajevszky S, Koszarska M, JAK2 46/1 haplotype analysis in myeloproliferative neoplasms and acute myeloid leukemia. Leukemia 2010;24:1809-13
  • Ramakrishnan V, Kimlinger T, Haug J, TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells. Am J Hematol 2010;85:675-86

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.