CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML)

Cancer Cell

Volumn 1, Issue 5, 2002, Pages 421-432

  Kelly, Louise M ^a,b   Yu, Jin Chen ^e   Boulton, Christina L ^a   Apatira, Mutiah ^e   Li, Jason ^e   Sullivan, Carol M ^e   Williams, Ifor ^c   Amaral, Sonia M ^a,b   Curley, David P ^a   Duclos, Nicole ^a,b   Neuberg, Donna ^d   Scarborough, Robert M ^e   Pandey, Anjali ^e   Hollenbach, Stanley ^e   Abe, Keith ^e   Lokker, Nathalie A ^e   Gilliland, D Gary ^a,b   Giese, Neill A ^e  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d DANA FARBER CANCER INSTITUTE   (United States)

^e MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [6 METHOXY 7 [3 (1 PIPERIDINYL)PROPOXY] 4 QUINAZOLINYL] 1 PIPERAZINECARBOXYLIC ACID (4 ISOPROPOXYPHENYL)AMIDE; FLT3 LIGAND; MITOGEN ACTIVATED PROTEIN KINASE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN SERINE THREONINE KINASE; STEM CELL FACTOR; TYROSINE; 4 (6 METHOXY 7 (3 PIPERIDIN 1 YLPROPOXY)QUINAZOLIN 4 YL)PIPERAZINE 1 CARBOXYLIC ACID (4 ISOPROPOXYPHENYL)AMIDE; 4-(6-METHOXY-7-(3-PIPERIDIN-1-YLPROPOXY)QUINAZOLIN-4-YL)PIPERAZINE-1-CARBOXYLIC ACID (4-ISOPROPOXYPHENYL)AMIDE; ANTINEOPLASTIC AGENT; CD135 ANTIGEN; CELL SURFACE RECEPTOR; ENZYME INHIBITOR; FLT3 PROTEIN, HUMAN; FLT3 PROTEIN, MOUSE; INTERLEUKIN 3; ONCOPROTEIN; PIPERAZINE DERIVATIVE; PROTEIN TYROSINE KINASE; QUINAZOLINE DERIVATIVE; STEM CELL FACTOR RECEPTOR;

ACUTE GRANULOCYTIC LEUKEMIA; ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHOSPHORYLATION; CANCER CELL CULTURE; CANCER INHIBITION; CELL GROWTH; CELL PROLIFERATION; CONTROLLED STUDY; DRUG EFFICACY; DRUG INHIBITION; DRUG POTENCY; ENZYME INHIBITION; IC 50; MOUSE; MOUSE STRAIN; NONHUMAN; NUDE MOUSE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; ANIMAL; BAGG ALBINO MOUSE; BONE MARROW CELL; BONE MARROW TRANSPLANTATION; CELL CULTURE; DRUG ANTAGONISM; DRUG EFFECT; ENZYMOLOGY; FLOW CYTOMETRY; GENETIC TRANSFECTION; GENETICS; HUMAN; IMMUNOBLOTTING; METABOLISM; MUTATION; PATHOLOGY; PHOSPHORYLATION; TANDEM REPEAT;

MURINAE; MUS MUSCULUS;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BONE MARROW CELLS; BONE MARROW TRANSPLANTATION; ENZYME INHIBITORS; FLOW CYTOMETRY; FMS-LIKE TYROSINE KINASE 3; HUMANS; IMMUNOBLOTTING; INTERLEUKIN-3; LEUKEMIA, MYELOCYTIC, ACUTE; MICE; MICE, INBRED BALB C; MICE, NUDE; MUTATION; PHOSPHORYLATION; PIPERAZINES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-KIT; QUINAZOLINES; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTORS, CELL SURFACE; RECEPTORS, PLATELET-DERIVED GROWTH FACTOR; TANDEM REPEAT SEQUENCES; TRANSFECTION; TUMOR CELLS, CULTURED;

EID: 0013102301     PISSN: 15356108     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1535-6108(02)00070-3     Document Type: Article

References (52)

1. Abu-Duhier, F.M., Goodeve, A.C., Wilson, G.A., Gari, M.A., Peake, I.R., Rees, D.C., Vandenberghe, E.A., Winship, P.R., and Reilly, J.T. (2000). FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Br. J. Haematol. 111, 190-195.
2. Abu-Duhier, F.M., Goodeve, A.C., Wilson, G.A., Care, R.S., Peake, I.R., and Reilly, J.T. (2001). Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia. Br. J. Haematol. 113, 983-988.
3. Benekli, M., Xia, Z., Donohue, K.A., Ford, L.A., Pixley, L.A., Baer, M.R., Baumann, H., and Wetzler, M. (2002). Constitutive activity of signal transducer and activator of transcription 3 protein in acute myeloid leukemia blasts is associated with short disease-free survival. Blood 99, 252-257.
4. Beran, M., Cao, X., Estrov, Z., Jeha, S., Jin, G., O'Brien, S., Talpaz, M., Arlinghaus, R.B., Lydon, N.B., and Kantarjian, H. (1998). Selective inhibition of cell proliferation and BCR-ABL phosphorylation in acute lymphoblastic leukemia cells expressing Mr 190,000 BCR-ABL protein by a tyrosine kinase inhibitor (CGP-57148). Clin. Cancer Res. 4, 1661-1672.
5. Birkenkamp, K.U., Geugien, M., Lemmink, H.H., Kruijer, W., and Vellenga, E. (2001). Regulation of constitutive STAT5 phosphorylation in acute myeloid leukemia blasts. Leukemia 15, 1923-1931.
6. Blume-Jensen, P., and Hunter, T. (2001). Oncogenic kinase signalling. Nature 411, 355-365.
7. Buchdunger, E., Cioffi, C.L., Law, N., Stover, D., Ohno-Jones, S., Druker, B.J., and Lydon, N.B. (2000). Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J. Pharmacol. Exp. Ther. 295, 139-145.
8. Carroll, M., Ohno-Jones, S., Tamura, S., Buchdunger, E., Zimmermann, J., Lydon, N.B., Gilliland, D.G., and Druker, B.J. (1997). CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood 90, 4947-4952.
9. bcr/abl gene of the Philadelphia chromosome. Science 247, 824-830.
10. Dorsey, J.F., Jove, R., Kraker, A.J., and Wu, J. (2000). The pyrido[2,3-d]pyrimidine derivative PD180970 inhibits p210Bcr-Abl tyrosine kinase and induces apoptosis of K562 leukemic cells. Cancer Res. 60, 3127-3131.
11. Dosil, M., Wang, S., and Lemischka, I.R. (1993). Mitogenic signalling and substrate specificity of the Flk2/Flt3 receptor tyrosine kinase in fibroblasts and interleukin 3-dependent hematopoietic cells. Mol. Cell. Biol. 13, 6572-6585.
12. Druker, B.J., and Lydon, N.B. (2000). Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J. Clin. Invest. 105, 3-7.
13. Druker, B.J., Tamura, S., Buchdunger, E., Ohno, S., Segal, G.M., Fanning, S., Zimmermann, J., and Lydon, N.B. (1996). Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med. 2, 561-566.
14. Druker, B.J., Sawyers, C.L., Kantarjian, H., Resta, D.J., Reese, S.F., Ford, J.M., Capdeville, R., and Talpaz, M. (2001a). Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N. Engl. J. Med. 344, 1038-1042.
15. Druker, B.J., Talpaz, M., Resta, D.J., Peng, B., Buchdunger, E., Ford, J.M., Lydon, N.B., Kantarjian, H., Capdeville, R., Ohno-Jones, S., and Sawyers, C.L. (2001b). Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031-1037.
16. Fang, G., Kim, C.N., Perkins, C.L., Ramadevi, N., Winton, E., Wittmann, S., and Bhalla, K.N. (2000). CGP57148B (STI-571) induces differentiation and apoptosis and sensitizes Bcr-Abl-positive human leukemia cells to apoptosis due to antileukemic drugs. Blood 96, 2246-2253.
17. Hayakawa, F., Towatari, M., Kiyoi, H., Tanimoto, M., Kitamura, T., Saito, H., and Naoe, T. (2000). Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene 19, 624-631.
18. Heldin, C.H., and Westermark, B. (1999). Mechanism of action and in vivo role of platelet-derived growth factor. Physiol. Rev. 79, 1283-1316.
19. Iida, M., Towatari, M., Nakao, A., Iida, H., Kiyoi, H., Nakano, Y., Tanimoto, M., Saito, H., and Naoe, T. (1999). Lack of constitutive activation of MAP kinase pathway in human acute myeloid leukemia cells with N-Ras mutation. Leukemia 13, 585-589.
20. Joensuu, H., Roberts, P.J., Sarlomo-Rikala, M., Andersson, L.C., Tervahartiala, P., Tuveson, D., Silberman, S., Capdeville, R., Dimitrijevic, S., Druker, B., and Demetri, G.D. (2001). Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N. Engl. J. Med. 344, 1052-1056.
21. Kelly, L.M., Liu, Q., Kutok, J.L., Williams, I.R., Boulton, C.L., and Gilliland, D.G. (2002). FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model. Blood 99, 310-318.
22. Kiyoi, H., Naoe, T., Nakano, Y., Yokota, S., Minami, S., Miyawaki, S., Asou, N., Kuriyama, K., Jinnai, I., Shimazaki, C., et al. (1999). Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood 93, 3074-3080.
23. Kottaridis, P.D., Gale, R.E., Frew, M.E., Harrison, G., Langabeer, S.E., Belton, A.A., Walker, H., Wheatley, K., Bowen, D.T., Burnett, A.K., et al. (2001). The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 98, 1752-1759.
24. Lavagna-Sevenier, C., Marchetto, S., Birnbaum, D., and Rosnet, O. (1998). The CBL-related protein CBLB participates in FLT3 and interleukin-7 receptor signal transduction in pro-B cells. J. Biol. Chem. 273, 14962-14967.
25. Liu, Q., Schwaller, J., Kutok, J., Cain, D., Aster, J.C., Williams, I.R., and Gilliland, D.G. (2000). Signal transduction and transforming properties of the TEL-TRKC fusions associated with t(12;15)(p13;q25) in congenital fibrosarcoma and acute myelogenous leukemia. EMBO J. 19, 1827-1838.
26. Lowenberg, B., Downing, J.R., and Burnett, A. (1999). Acute myeloid leukemia. N. Engl. J. Med. 341, 1051-1062.
27. Marchetto, S., Fournier, E., Beslu, N., Aurran-Schleinitz, T., Dubreuil, P., Borg, J.P., Birnbaum, D., and Rosnet, O. (1999). SHC and SHIP phosphorylation and interaction in response to activation of the FLT3 receptor. Leukemia 13, 1374-1382.
28. Matsuo, Y., MacLeod, R.A., Uphoff, C.C., Drexler, H.G., Nishizaki, C., Katayama, Y., Kimura, G., Fujii, N., Omoto, E., Harada, M., and Orita, K. (1997). Two acute monocytic leukemia (AML-M5a) cell lines (MOLM-13 and MOLM-14) with interclonal phenotypic heterogeneity showing MLL-AF9 fusion resulting from an occult chromosome insertion, ins(11;9)(q23;p22p23). Leukemia 11, 1469-1477.
29. Mauro, M.J., and Druker, B.J. (2001). STI571: targeting BCR-ABL as therapy for CML. Oncologist 6, 233-238.
30. Mizuki, M., Fenski, R., Halfter, H., Matsumura, I., Schmidt, R., Muller, C., Gruning, W., Kratz-Albers, K., Serve, S., Steur, C., et al. (2000). Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood 96, 3907-3914.
31. Nakao, M., Yokota, S., Iwai, T., Kaneko, H., Horiike, S., Kashima, K., Sonoda, Y., Fujimoto, T., and Misawa, S. (1996). Internal tandem duplication of the fits gene found in acute myeloid leukemia. Leukemia 10, 1911-1918.
32. Oetzel, C., Jonuleit, T., Gotz, A., van der Kuip, H., Michels, H., Duyster, J., Hallek, M., and Aulitzky, W.E. (2000). The tyrosine kinase inhibitor CGP 57148 (ST1 571) induces apoptosis in BCR-ABL-positive cells by down-regulating BCL-X. Clin. Cancer Res. 6, 1958-1968.
33. Rodriguez-Viciana, P., Warne, P.H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M.J., Waterfield, M.D., and Downward, J. (1994). Phosphatidylinositol- 3-OH kinase as a direct target of Ras. Nature 370, 527-532.
34. Rombouts, W.J., Blokland, I., Lowenberg, B., and Ploemacher, R.E. (2000). Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene. Leukemia 14, 675-683.
35. Rottapel, R., Turck, C.W., Casteran, N., Liu, X., Birnbaum, D., Pawson, T., and Dubreuil, P. (1994). Substrate specificities and identification of a putative binding site for PI3K in the carboxy tail of the murine Flt3 receptor tyrosine kinase. Oncogene 9, 1755-1765.
36. Savage, D.G., and Antman, K.H. (2002). Imatinib mesylate - a new oral targeted therapy. N. Engl. J. Med. 346, 683-693.
37. Schuringa, J.J., Wierenga, A.T., Kruijer, W., and Vellenga, E. (2000). Constitutive Stat3, Tyr705, and Ser727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6. Blood 95, 3765-3770.
38. Schwaller, J., Frantsve, J., Tomasson, M., Aster, J., Williams, I., Van Rompey, L., Marynen, P., Van Etten, R., Ilaria, R., and Gilliland, D.G. (1998). Transformation of hematopoietic cell lines to growth-factor independence and induction of a fatal myeloid and lymphoproliferative disease in mice by retrovirally transduced TEL/JAK2 fusion gene. EMBO J. 17, 5321-5333.
39. Stephens, L., Anderson, K., Stokoe, D., Erdjument-Bromage, H., Painter, G.F., Holmes, A.B., Gaffney, P.R., Reese, C.B., McCormick, F., Tempst, P., et al. (1998). Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science 279, 710-714.
40. Stirewalt, D.L., Kopecky, K.J., Meshinchi, S., Appelbaum, F.R., Slovak, M.L., Willman, C.L., and Radich, J.P. (2001). FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood 97, 3589-3595.
41. Stokoe, D., Stephens, L.R., Copeland, T., Gaffney, P.R., Reese, C.B., Painter, G.F., Holmes, A.B., McCormick, F., and Hawkins, P.T. (1997). Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 277, 567-570.
42. Talpaz, M., Silver, R.T., Druker, B.J., Goldman, J.M., Gambacorti-Passerini, C., Guilhot, F., Schiffer, C.A., Fischer, T., Deininger, M.W., Lennard, A.L., et al. (2002). Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 99, 1928-1937.
43. Testa, J.R., and Bellacosa, A. (2001). AKT plays a central role in tumorigenesis. Proc. Natl. Acad. Sci. USA 98, 10983-10985.
44. Tomasson, M.H., Williams, I.R., Hasserjian, R., Udomsakdi, C., McGrath, S.M., Schwaller, J., Druker, B., and Gilliland, D.G. (1999). TEL/PDGFβR induces hematologic malignancy in mice that responds to the tyrosine kinase inhibitor CGP57148. Blood 93, 1707-1714.
45. Towatari, M., Iida, H., Tanimoto, M., Iwata, H., Hamaguchi, M., and Saito, H. (1997). Constitutive activation of mitogen-activated protein kinase pathway in acute leukemia cells. Leukemia 11, 479-484.
46. Tse, K.F., Mukherjee, G., and Small, D. (2000). Constitutive activation of FLT3 stimulates multiple intracellular signal transducers and results in transformation. Leukemia 14, 1766-1776.
47. Whitman, S.P., Archer, K.J., Feng, L., Baldus, C., Becknell, B., Carlson, B.D., Carroll, A.J., Mrozek, K., Vardiman, J.W., George, S.L., et al. (2001). Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Res. 61, 7233-7239.
48. Yamamoto, Y., Kiyoi, H., Nakano, Y., Suzuki, R., Kodera, Y., Miyawaki, S., Asou, N., Kuriyama, K., Yagasaki, F., Shimazaki, C., et al. (2001). Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood 97, 2434-2439.
49. Yokota, S., Kiyoi, H., Nakao, M., Iwai, T., Misawa, S., Okuda, T., Sonoda, Y., Abe, T., Kahsima, K., Matsuo, Y., and Naoe, T. (1997). Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines. Leukemia 11, 1605-1609.
50. Yu, J.C., Lokker, N.A., Hollenbach, S., Apatira, M., Li, J., Betz, A., Sedlock, D., Oda, S., Nomoto, Y., Matsuno, K., et al. (2001). Efficacy of the novel selective platelet-derived growth factor receptor antagonist CT52923 on cellular proliferation, migration, and suppression of neointima following vascular injury. J. Pharmacol. Exp. Ther. 298, 1172-1178.
51. Zhang, S., Mantel, C., and Broxmeyer, H. (1999). Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their association with Grb2 and Shc in Baf3/Flt3 cells. J. Leukoc. Biol. 65, 372-380.
52. Zhou, B.P., Liao, Y., Xia, W., Zou, Y., Spohn, B., and Hung, M.C. (2001). HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat. Cell Biol. 3, 973-982.