Despite inhibition of hematopoietic progenitor cell growth in vitro, the tyrosine kinase inhibitor imatinib does not impair engraftment of human CD133+ cells into NOD/SCIDbeta2mNull mice.
[en] There is potential interest for combining allogeneic hematopoietic cell transplantation (HCT), and particularly allogeneic HCT with a nonmyeloablative regimen, to the tyrosine kinase inhibitor imatinib (Glivec; Novartis, Basel, Switzerland, http://www.novartis.com) in order to maximize anti-leukemic activity against Philadelphia chromosome-positive leukemias. However, because imatinib inhibits c-kit, the stem cell factor receptor, it could interfere with bone marrow engraftment. In this study, we examined the impact of imatinib on normal progenitor cell function. Imatinib decreased the colony-forming capacity of mobilized peripheral blood human CD133(+) cells but not that of long-term culture-initiating cells. Imatinib also decreased the proliferation of cytokine-stimulated CD133(+) cells but did not induce apoptosis of these cells. Expression of very late antigen (VLA)-4, VLA-5, and CXCR4 of CD133(+) cells was not modified by imatinib, but imatinib decreased the ability of CD133(+) cells to migrate. Finally, imatinib did not decrease engraftment of CD133(+) cells into irradiated nonobese diabetic/severe combined immunodeficient/beta2m(null) mice conditioned with 3 or 1 Gy total body irradiation. In summary, our results suggest that, despite inhibition of hematopoietic progenitor cell growth in vitro, imatinib does not interfere with hematopoietic stem cell engraftment.
Disciplines :
Hematology
Author, co-author :
Pirson, Laurence ✱; Centre Hospitalier Universitaire de Liège - CHU > Toxicologie clinique
Baron, Frédéric ✱; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Meuris, Nathalie ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
Giet, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Castermans, Emilie ; Université de Liège - ULiège > Département des sciences cliniques > Hématologie - Oncologie médicale
Greimers, Roland ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Di Stefano, Ivano
Gothot, André ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Beguin, Yves ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
✱ These authors have contributed equally to this work.
Language :
English
Title :
Despite inhibition of hematopoietic progenitor cell growth in vitro, the tyrosine kinase inhibitor imatinib does not impair engraftment of human CD133+ cells into NOD/SCIDbeta2mNull mice.
Publication date :
2006
Journal title :
Stem Cells
ISSN :
1066-5099
eISSN :
1549-4918
Publisher :
AlphaMed Company, Inc., Miamisburg, United States - Ohio
Volume :
24
Issue :
7
Pages :
1814-21
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
A. Gothot and Y. Beguin contributed equally to this work
Deininger MW, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood 2000;96:3343-3356.
Kurzrock R, Kantarjian HM, Druker BJ et al. Philadelphia chromosome-positive leukemias: From basic mechanisms to molecular therapeutics. Ann Intern Med 2003;138:819-830.
Druker BJ, Tamura S, Buchdunger E et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996;2:561-566.
Heinrich MC, Griffith DJ, Druker BJ et al. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 2000;96:925-932.
Mauro MJ, O'Dwyer M, Heinrich MC et al. STI571: A paradigm of new agents for cancer therapeutics. J Clin Oncol 2002;20:325-334.
Yee NS, Paek I, Besmer P. Role of kit-ligand in proliferation and suppression of apoptosis in mast cells: Basis for radiosensitivity of white spotting and steel mutant mice. J Exp Med 1994;179:1777-1787.
Ogawa M, Matsuzaki Y, Nishikawa S et al. Expression and function of c-kit in hemopoietic progenitor cells. J Exp Med 1991;174:63-71.
Haylock DN, To LB, Dowse TL et al. Ex vivo expansion and maturation of peripheral blood CD34+ cells into the myeloid lineage. Blood 1992;80:1405-1412.
Miller CL, Rebel VI, Helgason CD et al. Impaired steel factor responsiveness differentially affects the detection and long-term maintenance of fetal liver hematopoietic stem cells in vivo. Blood 1997;89:1214-1223.
Levesque JP, Leavesley DI, Niutta S et al. Cytokines increase human hemopoietic cell adhesiveness by activation of very late antigen (VLA)-4 and VLA-5 integrins. J Exp Med 1995;181:1805-1815.
Kim CH, Broxmeyer HE. In vitro behavior of hematopoietic progenitor cells under the influence of chemoattractants: Stromal cell-derived factor-1, steel factor, and the bone marrow environment. Blood 1998;91:100-110.
Patchen ML, Fischer R, Schmauder-Chock EA et al. Mast cell growth factor enhances multilineage hematopoietic recovery in vivo following radiation-induced aplasia. Exp Hematol 1994;22:31-39.
Neta R, Williams D, Selzer F et al. Inhibition of c-kit ligand/steel factor by antibodies reduces survival of lethally irradiated mice. Blood 1993;81:324-327.
Weiden PL, Flournoy N, Thomas ED et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic marrow grafts. N Engl J Med 1979;300:1068-1073.
Goldman JM, Gale RP, Horowitz MM et al. Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: Increased risk of relapse associated with T-cell depletion. Ann Intern Med 1988;108:806-814.
Appelbaum FR. Graft versus leukemia (GVL) in the therapy of acute lymphoblastic leukemia (ALL). Leukemia. 1997;11(suppl 4):S15-S17. Review.
Esperou H, Boiron JM, Cayuela JM et al. A potential graft-versus-leukemia effect after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Results from the French Bone Marrow Transplantation Society. Bone Marrow Transplant 2003;31:909-918.
Kottaridis PD, Milligan DW, Chopra R et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 2000;96:2419-2425.
Or R, Shapira MY, Resnick I et al. Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase. Blood 2003;101:441-445.
Wong R, Giralt SA, Martin T et al. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment of myeloid malignancies in patients older than 55 years of age. Blood 2003;102:3052-3059.
Childs R, Clave E, Contentin N et al. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: Full donor T-cell chimerism precedes alloimmune response. Blood 1999;94:3234-3241.
McSweeney PA, Niederwieser D, Shizuru J et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: Replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001;97:3390-3400.
Maris MB, Niederwieser D, Sandmaier BM et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood 2003;102:2021-2030.
Khouri IF, Lee MS, Saliba RM et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol 2003;21:4407-4412.
Baron F, Baker JE, Storb R et al. Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 2004;104:2254-2262.
Kerbauy FR, Storb R, Hegenbart U et al. Hematopoietic cell transplantation from HLA-identical sibling donors after low-dose radiation-based conditioning for treatment of CML. Leukemia 2005;19:990-997.
Baron F, Maris MB, Storer BE et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with chronic myeloid leukemia. Biol Blood Marrow Transplant 2005;11:272-279.
Baron F, Maris MB, Sandmaier BM et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol 2005;23:1993-2003.
Giet O, Van Bockstaele DR, Di S et al. Increased binding and defective migration across fibronectin of cycling hematopoietic progenitor cells. Blood 2002;99:2023-2031.
Huygen S, Giet O, Artisien V et al. Adhesion of synchronized human hematopoietic progenitor cells to fibronectin and vascular cell adhesion molecule-1 fluctuates reversibly during cell cycle transit in ex vivo culture. Blood 2002;100:2744-2752.
Druker BJ. STI571 (Gleevec) as a paradigm for cancer therapy. Trends Mol Med 2002;8:S14-S18.
Bartolovic K, Balabanov S, Hartmann U et al. Inhibitory effect of imatinib on normal progenitor cells in vitro. Blood 2004;103:523-529.
Deininger MW, Goldman JM, Lydon N et al. The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood 1997;90:3691-3698.
Holtz MS, Slovak ML, Zhang F et al. Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation. Blood 2002;99:3792-3800.
Giet O, Huygen S, Beguin Y et al. Cell cycle activation of hematopoietic progenitor cells increases very late antigen-5-mediated adhesion to fibronectin. Exp Hematol 2001;29:515-524.
Foguenne J, Huygen S, Greimers R et al. Modulation of homing properties of primitive progenitor cells generated by ex vivo expansion. Haematologica 2005;90:445-451.
Yong KL, Fahey A, Pizzey A et al. Influence of cell cycling and cell division on transendothelial migration of CD34+ cells. Br J Haematol 2002;119:500-509.
Levesque JP, Simmons PJ. Cytoskeleton and integrin-mediated adhesion signaling in human CD34+ hemopoietic progenitor cells. Exp Hematol 1999;27:579-586.
Hoepfl J, Miething C, Grundler R et al. Effects of imatinib on bone marrow engraftment in syngeneic mice. Leukemia 2002;16:1584-1588.
Mohty M, Blaise D, Olive D et al. Imatinib: The narrow line between immune tolerance and activation. Trends Mol Med 2005;11:397-402.
