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Advice and Resources for the Biotech Industry

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Flt3 Receptor and Ligand Articles

Lyman, S.D., James, L., Sleath, P.R., Zappone, J., Beckmann, M.P., and Bird, T. Characterization of the protein encoded by the flt3(flk2) receptor-like tyrosine kinase gene. Oncogene 8, 815-822, 1993.

Lyman, S.D., James, L., VandenBos, T., de Vries, P., Brasel, K., Gliniak, B., Hollingsworth, L. T. , Picha, K.S., McKenna, H.J., Splett, R.R., Fletcher, F.A., Maraskovsky, E., Farrah, T., Foxworthe, D., Williams, D.E., and Beckmann, M.P. Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor - A proliferative factor for primitive hematopoietic cells. Cell 75, 1157-1167, 1993.

Lyman, S.D., James, L., Johnson, L., Brasel, K., Escobar, S.S., Downey, H., de Vries, P., Splett, R.R., Beckmann, M.P., and McKenna, H. Cloning of the human homologue of the murine flt3 ligand: A growth factor for early hematopoietic progenitor cells. Blood 83, 2795-2801, 1994.

Lyman, S.D., James, L., Escobar, S., Downey, H., de Vries, K., Brasel, K., Stocking, K., Beckmann, M.P., Copeland, N.G., Cleveland, L.S., Jenkins, N.A., and Davison, B. Identification of soluble and membrane bound isoforms of the murine flt3 ligand generated by alternative splicing of mRNAs. Oncogene 10, 149-157, 1995.

Lyman, S.D., Brasel, K., Rousseau, A.-M., and Williams, D.E. The flt3 ligand: A hematopoietic stem cell factor whose activities are distinct from steel factor. Stem Cells 12, 99-110, 1994.

Lyman, S.D. and Williams, DE. Biology and Potential Clinical Applications of flt3 ligand. Current Opinion in Hematology 2, 177-181, 1995.

Lyman, S.D., Stocking, K., Davison, B. Fletcher, F., Johnson, L., and Escobar, S.S. Structural analysis of human and murine flt3 ligand genomic loci. Oncogene 11, 1165-1172, 1995.

Lyman, S.D. Biology of flt3 ligand and receptor. Int. J. Hematol. 62, 63-73, 1995.

Broxmeyer, H.E., Lu, L., Cooper, S., Ruggierei, L., Li, Z.-H., and
Lyman, S.D. Flt3 ligand stimulates/costimulates the growth of myeloid stem/progenitor cells. Exp. Hematol. 23, 1121-1129, 1995.

Hirayama, F.,
Lyman, S.D., Clark, S.C., and Ogawa, M. The flt3 ligand supports proliferation of lymphohemopoietic progenitors and early B-lymphoid progenitors. Blood 85, 1762-1768, 1995.

Jacobsen, S.E.W., Okkenhaug, C., Myklebust, J., Veiby, O.P., and
Lyman, S.D. The flt3 ligand potently and directly stimulates the growth and expansion of primitive murine bone marrow cells in vitro: Synergistic interactions with Interleukin (IL) 11, IL-12, and other hematopoietic growth factors. J. Exp. Med., 181, 1357-1363, 1995.

Jacobsen, S.E.W., Veiby, O.P., Myklebust, J., Okkenhaug, C, and
Lyman, S.D. Ability of flt3 ligand to stimulate the in vitro growth of primitive murine hematopoieitic progenitors is potently and directly inhibited by transforming growth factor-β and tumor-necrosis factor-α. Blood, 87, 5016-5026, 1996.

Rusten, L.S.,
Lyman, S.D., Veiby, O.P., and Jacobsen, S.E.W. The flt3 ligand is a direct and potent stimulator of the growth of primitive and committed human CD34+ bone marrow progenitor cells in vitro. Blood 87, 1317-1325, 1996.

Veiby, O.P., Jacobsen, F.W., Cui, L.,
Lyman, S.D., and Jacobsen, S.E.W. The flt3 Ligand promotes the survival of primitive hematopoietic progenitor cells with myeloid as well as B-lymphoid potential: suppression of apoptosis and counteraction by TNF-α and TGF-β. J. Immunol. 157, 2953-2960, 1996.

McKenna, H.J., de Vries, P., Brasel, K.,
Lyman, S.D., and Williams, D.E. Effect of flt3 ligand on the ex vivo expansion of human CD34+ hematopoietic progenitor cells. Blood 86, 3413-3420, 1995.

Brasel, K., Escobar, S., Anderberg, R., de Vries, P., Gruss, H.-J., and
Lyman, S.D. Expression of the flt3 receptor and its ligand on hematopoietic cells. Leukemia 9, 1212-1218, 1995.

Gabbianelli, M., Pelosi, E., Montesoro, E., Valtieri, M., Lucheti, L., Samoggia, P., Vitelli, L., Barberi, T., Testa, T.,
Lyman, S.D., and Peschle, C. Multi-level effects of flt3 ligand on human hematopoiesis: expansion of putative stem cells and proliferation of granulomonocytic progenitors/monocytic precursors. Blood 86, 1661-1670, 1995.

Lyman, S.D., Seaberg, M., Hanna, R., Abkowitz, J.L., Prchal, J., Schultz, J., and Shahidi, N.T. Plasma/serum levels of Flt3 ligand are low in normal individuals and are highly elevated in patients with Fanconi anemia and acquired aplastic anemias. Blood 86, 4091-4096, 1995.

Eder, M., Hemmati, P., Kalina, U., Ottmann, O.G., Hoelzer, D.,
Lyman, S.D., and Ganser, A. Effects of flt3 ligand and interleukin-7 on in vitro growth of acute lymphoblastic leukemia cells. Exp.. Hematology 24, 371-377, 1996.

Ray, R.J., Paige, C.J., Furlonger, C.,
Lyman, S.D., and Rottapel, R. Flt3 ligand supports the differentiation of early B cell progenitors in the presence of Interleukin-11 and Interleukin-7. Eur. J. Immunol. 26, 1504-1510, 1996.

McKenna, H.J., Smith, F.O., Brasel, K.,Hirschstein, D., Bernstein, I.D.,
Lyman, S.D., and Williams, D.E. Effects of flt3 ligand on acute myeloid and lymphocytic leukemic blast cells from children. Exp. Hematol. 24, 378-385, 1996.

Fujimoto, K.,
Lyman, S.D., Hirayama, F., and Ogawa, M. Isolation and characterization of primitive hematopoietic progenitors of murine fetal liver. Exp. Hematol. 24, 285-290, 1996.

Broxmeyer, H.E., Cooper, S., Etienne-Julan, M., Braun, S., Lu, L.,
Lyman, S.D., and Srivastava, A. Cord blood hematopoietic stem/progenitor cell growth and gene transduction using adeno-associated and retroviral vectors. Ontogeny of Hematopoiesis (Proceedings of the colloquium on "Foetal and neonatal hematopoiesis and the mechanisms of bone marrow failure". John Libbey Eurotext Limited, Montrouge, France) 235, 109-114, 1995.

Ohishi, K., Katayama, N., Itoh, R., Mahmud, N., Miwa, H., Kita, K., Minami, N., Shirakawa, S.,
Lyman, S.D., and Shiku, H. Accelerated cell cycling of hematopoietic progenitors by the flt3 ligand that is modulated by transforming growth factor-β. Blood 87, 1718-1727, 1996.

Takahira, H.,
Lyman, S.D., and Broxmeyer, H.E. Flt3 ligand prolongs survival of CD34+++ human umbilical cord blood myeloid progenitors in serum-depleted culture medium. Ann. Hematol. 72, 131-135, 1996.

Lisovsky, M., Braun, S.E., Ge, Y., Takahira, H., Lu, L., Savchenko, V.G.,
Lyman, S.D., and Broxmeyer, H.E. Flt3 ligand production by human bone marrow stromal cells. Leukemia 10, 1012-1018, 1996.

Veiby, O.P.,
Lyman, S.D., and Jacobsen, S.E.W. Combined signaling through interleukin-7 receptors and flt3 but not c-kit potently and selectively promotes B-cell commitment and differentiation from uncommitted murine bone marrow progenitor cells. Blood 88, 1256-1265, 1996.

Hjertson, M., Sundstrom, C.,
Lyman, S.D., Nilsson, K., and Nilsson, G. Stem cell factor, but not flt3 ligand, induces differentiation and activation of human mast cells. Exp. Hematol. 24, 748-754, 1996.

McKenna, H.J. and
Lyman, S.D. Biology of flt3 ligand, a novel regulator of hematopoietic stem and progenitor cells. in Bone Marrow Transplantation: Basic and Clinical Studies. (Ikehara, S., Takaku, F. and Good, R.A. editors). Springer-Verlag Tokyo, 85-93, 1996.

Wodnar-Filipowicz, A.,
Lyman, S.D., Gratwohl, A., Tichelli, A., Speck, B., and Nissen, C. Flt3 ligand level reflects hematopoietic progenitor cell function in aplastic anemia and chemotherapy-induced bone marrow aplasia. Blood 88, 4493-4499, 1996.

Maraskovsky, E., Brasel, K., Teepe, M., Roux, E.,
Lyman, S.D., Shortman, K.D., and McKenna, H.J. Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J. Exp. Med. 184, 1953-1962, 1996.

Turner, A.M., Lin, N.L., Issarachai, S.,
Lyman, S.D., and Broudy, V. FLT3 receptor expression on the surface of normal and malignant human hematopoietic cells. Blood 88, 3383-3390, 1996.

Ramsfjell, V., Borge, O.J., Veiby, O.P., Cardier, J., Murphy Jr., M.J.,
Lyman, S.D., Lok, S., and Jacobsen, S.E.W. Thrombopoietin, but not erythropoietin, directly stimulates multilineage growth of primitive murine bone marrow progenitor cells in synergy with early acting cytokines: Distinct interactions with the ligands for c-kit and FLT3. Blood 88, 4481-4492, 1996.

Brasel, K., McKenna, H.J., Morrissey, P.J., Charrier, K., Morris, A.E., Lee, C.C., Williams, D.E., and
Lyman, S.D. Hematologic effects of flt3 ligand in vivo in mice. Blood 88, 2004-2012, 1996.

Ku, H., Hirayama, F., Kato, T., Miyazaki, H., Aritomi, M., Ota, Y., D'Andrea, A.,
Lyman, S.D., and Ogawa, M. Soluble thrombopoietin receptor (mpl) and granulocyte colony-stimulating factor receptor directly stimulate proliferation of primitive hematopoietic progenitors of mice in synergy with Steel factor or the ligand for flt3/flk2. Blood, 88, 4124-4131, 1996.

Braun, S.E., Aronica, S.M., Ge, Y., Takahira, H., Etienne-Julan, M., Lu. L., Minden, M.,
Lyman, S.D., and Broxmeyer, H.E. Retroviral mediated gene transfer of Flt3 Ligand enhances proliferation and MAP kinase activity of AML5 cells. Exp. Hematol. 25, 51-56, 1997.

Ohmizono, Y., Sakabe, H., Kimura, T., Tanimukai, S., Matsumura, T.,
Lyman, S.D., and Sonoda, Y. Thrombopoietin augments ex vivo expansion of human cord blood derived hematopoietic progenitors in combination with stem cell factor and flt3 ligand. Leukemia 11, 524-530, 1997.

Yonemura, Y., Ku, H.,
Lyman, S.D., and Ogawa, M. In vitro expansion of hemtopoietic progenitors and maintenance of stem cells: Comparison between flt3/flk-2 ligand and kit ligand. Blood 89, 1915-1921, 1997.

Sonoda, Y., Kimura, T., Sakabe, H., Tanimukai, S., Ohmizono, Y., Nakagawa, S., Yokota, S.,
Lyman, S.D., and Abe, T. Human flt3 ligand acts on myeloid as well as multipotential progenitors derived from purified CD34+ blood progenitors expressing different levels of c-kit protein. Eur. J. Haematol. 58, 257-264, 1997.

Papayannopoulou, T., Nakamoto, B., Andrews, R.G.,
Lyman, S.D., and Lee, M.Y. In vivo effects of flt3/flk-2 ligand on mobilization of hemopoietic progenitors in primates and potent synergistic enhancement with Granulocyte Colony-Stimulating Factor. Blood 90, 620-629, 1997.

Wodnar-Filipowicz, A., Chklovskaia, E., Manz, C.Y.,
Lyman, S.D., and Nissen, C. Effect of flt3 ligand on in vitro growth and expansion of colony-forming bone marrow cells from patients with aplastic anemia. Exp. Hematol. 25, 573-581, 1997.

Strobl, H., Bello-Fernandez, C., Riedl, E., Pickl, W.F., Majdic, O.,
Lyman, S.D., and Knapp, W. Flt3 ligand in cooperation with Transforming Growth Factor-β1 potentiates in vitro development of Langerhans-type dendritic cells and allows single-cell dendritic cell cluster formation under serum-free conditions. Blood 90, 1425-1434, 1997.

Chen, K., Braun, S.,
Lyman, S., Fan, Y., Traycoff, C.M., Wiebke, E.A., Gaddy, J., Sledge, G., Broxmeyer, H.E., and Cornetta, K. Antitumor activity and immunotherapeutic properties of flt3-ligand in a murine breast cancer model. Cancer Res. 57, 3511-3516, 1997.

Brasel, K., McKenna, H.J., Charrier, K., Morrisey, P.J., Williams, D.E., and
Lyman, S.D. Flt3 ligand synergizes with Granulocyte-Macrophage Colony-Stimulating Factor or Granulocyte Colony-Stimulating Factor to mobilize hematopoietic progenitor cells into the peripheral blood of mice. Blood 90, 3781-3788, 1997.

Dooley, D.C., Xiao, M., Oppenlander, B.K., Plunkett, J.M., and
Lyman, S.D. Flt3 ligand enhances the yield of primitive cells after ex vivo cultivation of CD34+ CD38dim cells and CD34+ CD38 dim CD33 dim HLA-DR+ cells. Blood 90, 3903-3913, 1997.

Bello-Fernandez, C. Matyash, M., Strobl, H., Pickl W.F., Majdic, O.,
Lyman, S.D., and Knapp, W. Efficient retrovirus-mediated gene transfer of dendritic cells generated from CD34+ cord blood cells under serum-free conditions. Human Gene Therapy 8, 1651-1658, 1997.

Veiby, O.P., Borge, O.J., Martensson, A., Beck, E.X., Schade, A.E., Grzegorzewski, K.,
Lyman, S.D., Martensson, I.-L., and Jacobsen, S.E.W. Bidirectional effect of Interleukin-10 on early murine B-cell development: Stimulation of flt3-ligand plus Interleukin-7-dependent generation of CD19- proB cells from uncommitted bone marrow progenitor cells and growth inhibition of CD19+ proB cells. Blood 90, 4321-4331, 1997.

Ebihara, Y., Tsuji, K.,
Lyman, S.D., Sui, X., Yoshida, M., Muraoka, K., Yamada, K., Tanaka, R., and Nakahata, T. Synergistic action of flt3 and gp130 signalings in human hematopoiesis. Blood 90, 4363-4368, 1997.

Buhring, H.-J., Birnbaum, D., Brasel, K., Civin, C., Gotze, K.,
Lyman, S.D., Rappold, I., and Rosnet, O. CD135 (FLT3/FLK2/STK-1) Workshop Panel Report in Leukocyte Typing VI (Ed. by T. Kishimoto et al) pp. 875-879, Garland Publishing, Inc. New York, 1997.

Maraskovsky, E., Pulendran, B., Brasel, K., Teepe, M., Roux, E. R, Shortman, K.,
Lyman, S.D., McKenna, H. Dramatic numerical increase of functionally mature dendritic cells in flt3 ligand-treated mice. J. Adv. Exp. Med. Biol., 417 (Dendritic Cells in Fundamental and Clinical Immunology, Vol. 3), 33-40, 1997.

Kobayashi, M., Laver, J.H.,
Lyman, S.D., Kato, T., Miyazaki, H., and Ogawa, M. Thrombopoietin, steel factor and the ligand for flt3/flk2 interact to stimulate the proliferation of human hematopoietic progenitors in culture. Int. J. Hematol. 66, 423-434, 1997.

Lyman, S.D., Maraskovsky, E., and McKenna, H.J. Flt3 ligand, in The Cytokine Handbook, 3rd Edition, Angus Thomson, Editor, Academic Press, pp. 727-752, 1998.

Lyman, S.D. and Jacobsen, S.E.W. c-kit Ligand and flt3 Ligand: Stem/progenitor cell factors with overlapping yet distinct activities. Blood 91, 1101-1134, 1998.

Slanicka Krieger, M., Nissen, C., Manz, C.Y., Toksoz, D.,
Lyman, S.D., and Wodnar-Filipowicz, A. The membrane-bound isoform of stem cell factor synergizes with soluble flt3 ligand in supporting early hematopoietic cells in long-term cultures of normal and aplastic anemia bone marrow. Exp. Hematol. 26, 365-373, 1998.

Sakabe, H., Kimura, T., Tanimukai, S., Ohmizono, Y., Yokota, S, Hodohara,K., Okuda, T, Abe, T.,
Lyman, S.D., and Sonoda, Y. Haematopoietic action of flt3 ligand on cord blood-derived CD34-positive cells expressing different levels of flt3 or c-kit tyrosine kinase receptor: Comparison with stem cell factor. Eur. J. Haematol. 60, 297-306, 1998.

Graddis, T.J., Brasel, K, Friend, D., Srinivasan, S.,
Lyman, S.D., March, C.J., and McGrew, J.T. Structure-function analysis of human flt3 ligand-flt3 receptor interactions using a rapid functional screen. J. Biol. Chem. 273, 17626-17633, 1998.

Lyman, S.D. Biologic effects and potential clinical applications of flt3 ligand. Current Opinion in Hematology 5, 192-196, 1998.

Gratwohl, A., John, L., Baldomero, H., Roth, J, Tichelli, A., Nissen, C.,
Lyman, S.D., and Wodnar-Filipowicz, A. Flt-3 ligand provides hematopoietic protection from total body irradiation in rabbits. Blood 92, 765-769, 1998.

Hawley, T.S., Fong, A.Z.C., Griesser, H.,
Lyman, S.D., and Hawley, R.G. Leukemic predisposition of mice transplanted with gene-modified hematopoietic precursors expressing flt3 ligand. Blood 92, 2003-2011, 1998.

Balduini, A., Braun, S.E., Cornetta, K.,
Lyman, S.D., and Broxmeyer, H. Comparative effects of retroviral mediated gene transfer into primary human stromal cells of flt3 ligand, IL-3, and GM-CSF on production of cord blood progenitor cells in long term culture. Stem Cells 16, 37-49, 1999.

Pless, M., Wodnar-Filipowicz, A., John, L., Baldomero, H.,
Lyman, S.D., Nissen, C, and Gratwohl, A. Synergy of growth factors during mobilization of peripheral blood precursor cells with recombinant human flt3-ligand and Granulocyte Colony-Stimulating Factor in rabbits. Exp. Hematology 27, 155-161, 1998.

Chklovskaia, E., Jansen, W., Nissen, C.,
Lyman, S.D., Rahner, C., Landmann, L., Wodnar-Filipowicz, A. Mechanism of Flt3 ligand expression in bone marrow failure: translocation from intracellular stores to the surface of T lymphocytes following chemotherapy-induced suppression of hematopoiesis. Blood 93, 2595-2604, 1999.

Zwierzina, H., Anderson, J.E , Rollinger-Holzinger, I., Torok-Storb, B., Nuessler, V., and
Lyman, S.D. Endogenous flt3 ligand serum levels are associated with disease stage in patients with myelodysplastic syndromes. Leukemia 13, 553-557, 1999.

Banu, N., Deng, B.,
Lyman, S.D., and Avraham, H. Modulation of hematopoietic progenitor development by flt-3 ligand. Cytokine 11, 679-688, 1999.

McKenna, H.J., Stocking, K., Miller, B., Brasel, K., De Smedt, T., Maraskovsky, E., Maliszewski, C., Lynch, D., Smith, J., Pulendran, B., Roux, E., Teepe, M.,
Lyman, S.D., and Peschon, J. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood 95, 3489-3497, 2000.

Maraskovsky, E.,
Lyman, S.D., Maliszewski, C.R., and Lynch, D.H. Flt-3 and Flt-3 ligand, in Principles and Practice of the Biologic Therapy of Cancer, 3rd Edition., Steven Rosenberg, Ed. Lipincott, Williams, and Wilkins, Philadelphia, 875-889, 2000.

Pfister, O., Chklovskaia, E., Jansen, W., Meszaros, K., Nissen, C., Rahner, C., Hurwitz, N., Bogatcheva, N.,
Lyman, S.D., and Wodnar-Filipowicz, A. Chronic overexpression of membrane-bound flt3 ligand by T lymphocytes in severe aplastic anemia. Br. J. Haematol. 109, 211-220, 2000.

Lyman, S.D., and McKenna, H.J. Flt3 ligand, in The Cytokine Handbook, 4th Edition, Angus Thomson, Editor, Academic Press, Volume 2, pp. 989-1010, 2003.