Effects of imatinib on bone marrow engraftment in syngeneic mice.
Chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemias arise from the genetic reciprocal translocation t(9;22), forming the BCR-ABL fusion gene. These lead to the expression of the constitutively active tyrosine kinase BCR-ABL, which is the causative oncogene for these leukemias. Allogeneic bone marrow transplantation (BMT) or stem cell transplantation (SCT) is currently considered the only curative treatment for chronic myeloid leukemia (CML). Recently, the selective tyrosine kinase inhibitor imatinib mesylate (Glivec, formerly STI-571) has been shown to induce durable hematologic and major cytogenetic responses in a high percentage of patients with chronic phase CML. In patients with advanced disease remissions are transient and most patients relapse despite continued imatinib treatment. Some of these patients go on to receive allogeneic BMT or SCT, during which administration of imatinib is usually discontinued as it is believed to interfere with bone marrow engraftment. In this study, we examined the effect of imatinib on hematopoietic engraftment in a syngeneic mouse model. We found that imatinib has no significant influence on hematopoietic recovery in lethally irradiated mice in vivo. Thus, our results suggest that continued administration of imatinib in the course of BMT or SCT may be a feasible therapeutic regimen.
Department of Internal Medicine III, Laboratory of Leukemogenesis, Technical University of Munich, Munich, Germany.
J
J
Hoepfl
C
C
Miething
R
R
Grundler
K S
KS
Götze
C
C
Peschel
J
J
Duyster
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells; D000068877:Imatinib Mesylate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010879:Piperazines / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D014185:Transplantation, Isogeneic; D014916:Whole-Body Irradiation
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit