Rationalizing autotransplant strategies for chronic myeloid leukemia.
The molecular genetic basis of chronic myeloid leukemia (CML) is well-defined, but until recently therapeutic approaches have been largely empiric. Conventional chemotherapy and interferon offer palliation, but only bone marrow transplantation provides for cure. Because the majority of CML patients are not candidates for allogeneic transplantation, autologous strategies have emerged as an alternative. Data from murine models of CML provide insights into the mechanisms by which autotransplant might be effective in the treatment of CML. Further dissection of the molecular pathways by which the BCR/ABL protein can induce leukemia offers the promise of a more targeted, rationally-designed therapy. When used for remission maintenance therapy following autologous bone marrow transplantation, specific inhibitors of BCR/ABL should provide for long term disease-free survival.
Daley
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Division of Hematology-Oncology, Massachusetts General Hospital, Boston and Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
D000818:Animals; D001752:Blast Crisis / Q000235:genetics / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000379:methods*; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D002999:Clone Cells / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D016044:Fusion Proteins, bcr-abl / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007942:Leukemia, Experimental / Q000235:genetics / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology; D015398:Signal Transduction; D014182:Transplantation, Autologous / Q000379:methods*
D016044:Fusion Proteins, bcr-abl