Original Article

You have full text access to this OnlineOpen article

The role of Src in solid and hematologic malignancies

Development of new-generation Src inhibitors

  1. Ricardo H. Alvarez MD1,
  2. Hagop M. Kantarjian MD2,
  3. Jorge E. Cortes MD2,†,*

Article first published online: 19 SEP 2006

DOI: 10.1002/cncr.22215

Issue

Cancer

Cancer

Volume 107, Issue 8, pages 1918–1929, 15 October 2006

Additional Information

How to Cite

Alvarez, R. H., Kantarjian, H. M. and Cortes, J. E. (2006), The role of Src in solid and hematologic malignancies. Cancer, 107: 1918–1929. doi: 10.1002/cncr.22215

Author Information

  1. 1

    Department of Internal Medicine, The University of Texas School of Medicine, Houston, Texas

  2. 2

    Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

  1. †

    Fax: (713) 794-4297

*Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 428, Houston, TX 77030

Publication History

  1. Issue published online: 3 OCT 2006
  2. Article first published online: 19 SEP 2006
  3. Manuscript Accepted: 17 JUL 2006
  4. Manuscript Revised: 10 JUN 2006
  5. Manuscript Received: 4 APR 2006

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (327K)

REFERENCES

  • 1
    Rous P. A sarcoma of the fowl transmissible by an agent separable for the tumor cells. J Exp Med. 1911; 13: 397–411.
  • 2
    Rubin H. Quantitative relations between causative virus and cell in the Rous no. 1 chicken sarcoma. Virology. 1956; 6: 669–688.
  • 3
    Martin GS. Rous sarcoma virus: a function required for the maintenance of the transformed state. Nature. 1970; 227: 1021–1023.
  • 4
    Thomas SM, Brugge JS. Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol. 1997; 13: 513–609.
  • 5
    Bjorge JD, Jakymiw A, Fujita DJ. Selected glimpses into the activation and function of Src kinase. Oncogene. 2000; 19: 5620–5635.
  • 6
    Haskell MD, Slack JK, Parsons JT, et al. c-Src tyrosine phosphorylation of epidermal growth factor receptor, P190 RhoGAP, and focal adhesion kinase regulates diverse cellular processes. Chem Rev. 2001; 101: 2425–2440.
  • 7
    Sawyer TK. Src homology-2 domains: structure, mechanism and drug discovery. Biopolymers. 1998; 47: 243– 261.
    Direct Link:
  • 8
    Johnson LN, Noble MLM, Owen DJ. Active and inactive protein kinases: structural basis for regulation. Cell. 1996; 85: 149–158.
  • 9
    Roche S, Fumagalli S, Courtneidge SA. Requirement for Src family protein tyrosine kinases in G2 for fibroblast cell division. Science. 1995; 269: 1567–1569.
  • 10
    Prathapam T, Tegen S, Oskarsson T, Trumpp A, Martin GS. Activated Src abrogates the Myc requirement for the G0/G1 transition but not for the G1/S transition. Proc Natl Acad Sci USA. 2006; 103: 2695–700.
  • 11
    Cooper JA, Gould KL, Cartwright CA, et al. Tyr527 is phosphorylated in pp60c-src: implications for regulation. Science. 1986; 231: 1431–1434.
  • 12
    Roskoski RJr. Src kinase regulation by phosphorylation and dephosphorylation. Biochem Biophys Res Commun. 2005; 331: 1–14.
  • 13
    Nakagawa S, Tanaka H, Suzuki H, et al. Overexpression of the CSK gene suppresses tumor metastasis in vivo. Int J Cancer. 2000; 88: 384–391.
    Direct Link:
  • 14
    Lee BC, Lee TH, Zagozdzon R, Avraham S, Usheva A, Avraham HK. Carboxyl-terminal Src kinase homologous kinase negatively regulates the chemokine receptor CXCR4 through YY1 and impairs CXCR4/CXCL12 (SDF-1α)-mediated breast cancer cell migration. Cancer Res. 2005; 65: 2840–2845.
  • 15
    Alonso G, Koegl M, Mazurenko N, et al. Sequence requirements for binding of Src family tyrosine kinases to activated growth factor receptors. J Biol Chem. 1995; 270: 9840–9848.
  • 16
    Schlaepfer DD, Jones KC, Hunter T, et al. Multiple Grb2-mediated integrin-stimulated signaling pathways to ERK2/mitogen-activated protein kinase: summation of both c-Src- and focal adhesion kinase initiated tyrosine phosphorylation events. Mol Cell Biol. 1998; 18: 2571–2585.
  • 17
    Summy JM, Gallick GE. Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev. 2003; 22: 337–358.
  • 18
    Cartwright CA, Eckhart W, Simon S, et al. Cell transformation by pp60c-src mutated in the carboxyterminal regulatory domain. Cell. 1987; 49: 83–91.
  • 19
    Parsons JT, Parsons SJ. Src family protein tyrosine kinases: cooperating with growth factor and adhesion signaling pathways. Curr Opin Cell Biol. 1997; 9: 187–192.
  • 20
    Twamley-Stein GM, Pepperkok R, Ansorge W, et al. The Src family tyrosine kinases are required for platelet-derived growth factor-mediated signal transduction in NIH 3T3 cells. Proc Natl Acad Sci USA. 1993; 90: 7696–7700.
  • 21
    Blake RA, Broome MA, Liu X, et al. SU6656, a selective Src family kinase inhibitor, used to probe growth factor signaling. Mol Cell Biol. 2000; 20: 9018–9027.
  • 22
    DeMali KA, Kazlauskas A. Activation of Src family members is not required for the platelet-derived growth factor beta receptor to initiate mitogenesis. Mol Cell Biol. 1998; 18: 2014–2022.
  • 23
    Roche S, Koegl M, Barone MV, et al. DNA synthesis induced by some but not all growth factors requires Src family protein tyrosine kinases. Mol Cell Biol. 1995; 15: 1102–1109.
  • 24
    Gullick WJ, Love SB, Writh C, et al. c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes. Br J Cancer. 1992; 63: 954–961.
  • 25
    Biscardi JS, Ishizawar RC, Silva CM, et al. Tyrosine kinase signaling in breast cancer: Epidermal growth factor receptor and c-Src interactions in breast cancer. Breast Cancer Res. 2000; 2: 203–210.
  • 26
    Daub H, Wallasch C, Lankenau A, et al. Signal characteristics of G protein-transactivated EGF receptor. EMBO J. 1997; 16: 7032–7044.
  • 27
    Ware MF, Tice DA, Parsons SJ, et al. Overexpression of cellular Src in fibroblasts enhances endocytic internalization of epidermal growth factor receptor. J Biol Chem. 1997; 272: 30185–30190.
  • 28
    Hall A. Rho GTPases and the actin cytoskeleton. Science. 1998; 279: 509–514.
  • 29
    Chang JH, Gill S, Settleman J, et al. c-Src regulates the simultaneous rearrangement of actin cytoskeleton, p190RhoGAP, and p120RasGAP following epidermal growth factor stimulation. J Cell Biol. 1995; 130: 355–368.
  • 30
    Avizienyte E, Frame MC. Src and FAK signaling controls adhesion fate and the epithelial-to-mesenchymal transition. Curr Opin Cell Biol. 2005; 17: 547–547.
  • 31
    Potter MD, Barbero S, Cheresh DA. Tyrosine phosphorylation of VE-cadherin prevents binding of p120-and-beta catenin and maintains cellular mesenchymal state. J Biol Chem. 2005; 280: 31906–31912.
  • 32
    Zamir E, Geiger B. Molecular complexity and dynamics of cell-matrix adhesions. J Cell Sci. 2001; 114: 3583–3590.
  • 33
    Sastry SK, Burridge K. Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Exp Cell Res. 2000; 261: 25–36.
  • 34
    Schaller MD. Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim Biophys Acta. 2001; 1540: 1–21.
  • 35
    Owens LV, Xu L, Craven RJ, et al. Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res. 1995; 55: 2752–2755.
  • 36
    Irby RB, Yeatman TJ. Role of Src expression and activation in human cancer. Oncogene. 2000; 19: 5636–5642.
  • 37
    Brown MT, Cooper JA. Regulation, substrates and functions of Src. Biochim Biophys Acta. 1996; 1287(2–3): 121–149.
  • 38
    Bolen JB, Veillette A, Schwartz AM, et al. Activation of pp60 (c-Src) protein kinase activity in human colon carcinoma. Proc Natl Acad Sci USA. 1987; 84: 2251–2255.
  • 39
    Cartwright CA, Meisler AI, Eckhart W. Activation of the pp60 (c-Src) protein kinase is an early event in colonic carcinogenesis. Proc Natl Acad Sci USA. 1990; 87: 558–562.
  • 40
    Termuhlen PM, Curley SA, Talamonty MS, et al. Site-specific differences in pp60 (c-Src) activity in human colorectal metastases. J Surg Res. 1993; 54: 293–298.
  • 41
    Irby RB, Mao W, Coppola D, et al. Activating SRC mutation in a subset of advanced human colon cancer. Nat Genet. 1999; 21: 187–190.
  • 42
    Daigo Y, Furukawa Y, Kawasoe T, et al. Absence of genetic alteration at codon 531 of the human c-Src gene in 479 advanced colorectal cancers from Japanese and Caucasian patients. Cancer Res. 1999; 59: 4222–4224.
  • 43
    Wang NM, Yeh KT, Tsai CH, Chen SJ, Chang JG. No evidence of correlation between mutation at codon 531 of src and the risk of colon cancer in Chinese. Cancer Lett. 2000; 150: 201–204.
  • 44
    Allgayer H, Boyd DD, Heiss MM, et al. Activation of Src kinase in primary colorectal carcinoma: an indicator of poor clinical prognosis. Cancer. 2002; 94: 344–351.
    Direct Link:
  • 45
    Han NM, Curley SA, Gallick GE, et al. Differential activation of pp60(c-Src) and pp62(c-Yes) in human colorectal carcinoma and liver metastasis. Clin Cancer Res. 1996; 2: 1397–1404.
  • 46
    Ottenhoff-Kalff AE, Rijksen G, van Beurden EA, et al. Characterization of protein tyrosine kinases from human breast cancer: involvement of the c-Src oncogene product. Cancer Res. 1992; 52: 4773–4778.
  • 47
    Muthuswamy SK, Siegel PM, Dankort DL, et al. Mammary tumors expressing the neu proto-oncogene possesses elevated c-Src tyrosine kinase activity. Mol Cell Biol. 1994; 14: 735–743.
  • 48
    Biscardi JS, Belsches AP, Parsons SJ, et al. Characterization of human epidermal growth factor receptor and c-Src interaction in human breast tumor cells. Mol Carcinog. 1998; 21: 261–272.
    Direct Link:
  • 49
    Tan M, Li P, Klos KS, et al. ErbB2 promotes Src synthesis and stability: novel mechanisms of Src activation that confer breast cancer metastasis. Cancer Res. 2005; 65: 1858–1867.
  • 50
    Palacios EH, Weiss A. Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Oncogene. 2004; 23: 7990–8000.
  • 51
    Danhauser-Riedl S, Warmurth M, Druker BJ, et al. Activation of Src kinases p53/56lyn and p59hck by p210bcr-abl in myeloid cells. Cancer Res. 1996; 56: 3589–3596.
  • 52
    Warmuth M, Bergmann M, Priess A, et al. The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr. J Biol Chem. 1997; 272: 33260–33270.
  • 53
    Lionberger JM, Wilson MB, Smithgall TE. Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck. J Biol Chem. 2000; 275: 18581–18585.
  • 54
    Ptasznik A, Urbanowska E, Chinta S, et al. Crosstalk between BCR/ABL oncoprotein and CXCR4 signaling through a Src family kinase in human leukemia cells. J Exp Med. 2002; 196: 667–678.
  • 55
    Hu Y, Liu Y, Pelletier S, et al. Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Nat Genet. 2004, 36: 453–461.
  • 56
    Donato NJ, Wu JY, Stapley J, et al. BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood. 2003; 101: 690–698.
  • 57
    Marth JD, Overell RW, Meier KE, et al. Translational activation of the lck proto-oncogene. Nature. 1988; 332: 171–173.
  • 58
    Jayaraman T, Marks AR. T cells deficient in inositol 1,4,5-trisphosphate receptor are resistant to apoptosis. Mol Cell Biol. 1997; 17: 3005–3012.
  • 59
    Mazurenko NN, Kogan EA, Zborovskaya IB, et al. Expression of pp60c-src in human small cell and non-small cell lung carcinomas. Eur J Cancer. 1992; 28: 372–377.
  • 60
    Wiener JR, Nakano K, Kuzrock RP, et al. Decreased Src tyrosine kinase activity inhibits malignant human ovarian cancer tumor growth in a nude mouse model. Clin Cancer Res. 1999; 5: 2164–2170.
  • 61
    Kumble S, Omary MB, Cartwright CA, et al. Src activation in malignant and premalignant epithelia of Barrett's esophagus. Gastroenterology. 1997; 112: 348–356.
  • 62
    Takeshima E, Hamaguchi M, Watanabe T, et al. Aberrant elevation of tyrosine-specific phosphorylation in human gastric cancer cells. Jpn J Cancer Res. 1991; 82: 1428–1435.
  • 63
    Lutz MP, Esser IB, Flossmann-Kast BB, et al. Overexpression and activation of the tyrosine kinase Src in human pancreatic carcinoma. Biochem Biophys Res Commun. 1998; 243: 503–508.
  • 64
    Hanke JH, Gardner JP, Dow RL, et al. Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. J Biol Chem. 1996; 271: 695–701.
  • 65
    Suzuki S, Hayashi Y, Wang Y, et al. Urokinase type plasminogen activator receptor expression in colorectal neoplasias. Gut. 1998; 43: 798–805.
  • 66
    Boyd DD, Wang H, Avila H, et al. Combination of a Src kinase inhibitor with a novel pharmacological antagonist of the urokinase receptor diminished in vitro colon cancer invasiveness. Clin Cancer Res. 2004; 10: 1545–1555.
  • 67
    Goan YG, Zhou B, Hu E, et al. Overexpression of ribonucleotide reductase as a mechanism of resistance to 2,2-difluorodeoxycytidine in the human KB cancer cell line. Cancer Res. 1999; 59: 4204–4207.
  • 68
    Duxbury MS, Ito H, Zinner MJ, et al. Inhibition of Src tyrosine kinase impairs inherent and acquired gemcitabine resistance in human pancreatic adenocarcinoma cells. Clin Cancer Res. 2004; 10: 2307–2318.
  • 69
    Nam JS, Ino Y, Sakamoto M, et al. Src family kinase inhibitor PP2 restores the E-cadherin/catenin cell adhesion system in human cancer cells and reduces cancer metastasis. Clin Cancer Res. 2002; 8: 2430–2436.
  • 70
    Javerzat S, Auguste P, Bikfalvi A. The role of fibroblast growth factors in vascular development. Trends Mol Med. 2002; 8: 483–489.
  • 71
    Kumar P, Amin MA, Harlow LA, et al. Src and phosphatidylinositol 3-kinase mediate soluble E-selectin-induced angiogenesis. Blood. 2003; 101: 3960–3968.
  • 72
    Altmann E, Missbach M, Green J, et al. Pyrrolidinyl- and 7-piperidinyl-5-aryl-pyrrolo[2,3-d]pyrimidines—potent inhibitors of the tyrosine kinase c-Src. Bioorg Med Chem Lett. 2001; 11: 853–856.
  • 73
    Missbach M, Jeschke M, Feyen J, et al. Novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo. Bone. 1999; 24: 437–449.
  • 74
    Recchia I, Rucci N, Funari A, et al. Reduction of c-Src activity by substituted 5,7-diphenyl-pyrrolo[2,3-d]-pyrimidines induces osteoclast apoptosis in vivo and in vitro. Involvement of ERK1/2 pathway. Bone. 2004; 34: 65–79.
  • 75
    Warmuth M, Simon N, Mitina O, et al. Dual-specific Src and Abl kinase inhibitors, PP1 and CGP76030, inhibit growth and survival of cells expressing imatinib mesylate-resistant Bcr-Abl kinases. Blood. 2003; 101: 664–672.
  • 76
    Panek RL, Lu GH, Klutchko SR, et al. In vitro pharmacological characterization of PD 166285, a new nanomolar potent and broadly active protein tyrosine kinase inhibitor. J Pharmacol Exp Ther. 1997; 283: 1433–1444.
  • 77
    Roginskaya V, Zuo S, Caudell E, et al. Therapeutic targeting of Src-kinase Lyn in myeloid leukemic cell growth. Leukemia. 1999; 13: 855–861.
  • 78
    Moasser MM, Srethapakdi M, Sachar KS, et al. Inhibition of Src kinases by a selective tyrosine kinase inhibitor causes mitotic arrest. Cancer Res. 1999; 59: 6145–6152.
  • 79
    Wisniewski D, Lambek CL, Liu C, et al. Characterization of potent inhibitors of the Bcr-Abl and the c-Kit receptor tyrosine kinases. Cancer Res. 2002; 62: 4244–4255.
  • 80
    Nagar B, Bornmann WG, Pellicena P, et al. Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). Cancer Res. 2002; 62: 4236–4243.
  • 81
    Dorsey JF, Jove R, Kraker AJ, et al. The pyrido[2,3-d]pyrimidine derivate PD180970 inhibits p210Bcr-Abl tyrosine kinase and induces apoptosis of K652 leukemic cells. Cancer Res. 2000; 60: 3127–3131.
  • 82
    La Rosse P, Corbin AS, Stoffregen EP, et al. Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571). Cancer Res. 2002; 62: 7149–7153.
  • 83
    Gu H, Pratt JC, Burakoff SJ, et al. Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation. Mol Cell. 1999; 2: 729–740.
  • 84
    Kraker AJ, Hartl BG, Amar A, et al. Biochemical and cellular effects of c-src selective pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors. Biochem Pharmacol. 2000; 60: 885–898.
  • 85
    Nimmanapally R, O'Bryan E, Huang M, et al. Molecular characterization and sensitivity of STI-571 (imatinib mesylate-Gleevec)-resistant, Brc-Abl-positive, human acute leukemia cells to SRC kinase inhibitor PD180970 and 17-allylamino-17-demethoxygeldanamycin. Cancer Res. 2002; 62: 5761–5769.
  • 86
    von Bubnoff N, Veach DR, Miller T, et al. Inhibition of wild-type and mutant Bcr-Abl by pyrimidine-type small molecule kinase inhibitors. Cancer Res. 2003; 63: 6395–6404.
  • 87
    Boschelli DH, Ye F, Wang YD, et al. Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J Med Chem. 2001; 44: 3965–3977.
  • 88
    Golas JM, Arndt K, Etienne C, et al. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res. 2003; 63: 375–381.
  • 89
    Nagar B, Hantschel O, Young M, et al. Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell. 2003; 112: 859–871.
  • 90
    Tokarshi JS, Newitt J, Lee FY, et al. The crystal structure of Abl kinase with BMS354825, a dual Src/Abl kinase inhibitor. Blood. 2004; 104: 160a. Abstract 553.
  • 91
    Burgess MR, Skaggs BJ, Shah NP, et al. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance. Proc Natl Acad Sci USA. 2005; 102: 3395–3400.
  • 92
    Shah NP, Tran C, Lee FY, et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004; 305: 399–401.
  • 93
    O'Hare T, Walters DK, Stoffregen EP, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005; 65: 4500–4505.
  • 94
    Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Eng J Med. 2006; 354: 2531–2596.
  • 95
    Shah N, Sawyers CL, Kantarjian H, et al. Correlation of clinical response to BMS-354825 with BCR-ABL mutation status in imatinib-resistant patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-associated acute lymphoblastic leukemia (Ph+ ALL). J Clin Oncol. 2005; 16S: 564s. Abstract 6521.
  • 96
    Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Eng J Med. 2006; 354: 2542–2596.
  • 97
    O'Hare T, Pollock R, Stoffregen EP, et al. Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. Blood. 2004; 104: 2532–2539.
  • 98
    Kanerva J, Nwawka O, Hwang K, et al. A potent Src/Abl kinase inhibitor (AP23464) potently inhibits the growth of myeloid leukemic cells characterized by Flt3-ITD expression, GM-CSF dependency, or G-CSF responsiveness via and Abl-independent mechanism. Blood. 2004; 104: 202b. Abstract 4479.
  • 99
    Corbin AS, Demehri S, Griswold IJ, et al. In vitro and in vivo activity of the Src/Abl kinase inhibitor AP23464 and analogs against activation loop mutants of KIT. Blood. 2004; 104: 227a. Abstract 793.
  • 100
    Shakespeare WC, Metcalf CAIII, Wang Y, et al. Novel bone-targeted Src tyrosine kinase inhibitor drug discovery. Curr Opin Drug Discov Dev. 2003; 6: 729–741.
  • 101
    Kimura S, Naito H, Segawa H, et al. NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia. Blood. 2005; 106: 3948–3954.
  • 102
    Naito H, Kimura S, Nakaya Y, et al. In vivo antiproliferative effect of NS-187, a dual Bcr-Abl/Lyn tyrosine kinase inhibitor, on leukemic cells harbouring Abl kinase domain mutations. Leukemia Res. 2006 [Epub ahead of print].
  • 103
    Hochhaus A, Kantarjian H, Baccarani M, et al. Dasatinib in patients with chronic phase chronic myeloid leukemia who are resistant or intolerant to imatinib: results of the CA180013 “START-C” Study. J Clin Oncol. 2006; 24: 339a. Abstract 6508.
  • 104
    Talpaz M, Apperley JF, Kim DW, et al. Dasatinib in patients with accelerated phase chronic myeloid leukemia who are resistant or intolerant to imatinib: results of the CA180005 “START-A” Study. J Clin Oncol. 2006; 24: 343a. Abstract 6526.
  • 105
    Coutre S, Martinelli G, Dombret H, et al. Dasatinib in patients with chronic myeloid leukemia in lymphoid blast crisis or Philadelphia-chromosome positive acute lymphoblastic leukemia who are imatinib-resistant or intolerant: the CA180015 ‘START-L’ Study. J Clin Oncol. 2006; 24: 344a. Abstract 6528.
  • 106
    Cortes J, Kim DW, Rosti G, et al. Dasatinib in patients with chronic myeloid leukemia in myeloid blast crisis who are imatinib-resistant or intolerant: the CA180006 ‘START-B’ Study. J Clin Oncol. 2006; 24: 344a. Abstract 6529.
View Full Article (HTML) Get PDF (327K)