title: Biology and treatment of chronic myeloid leukemia.
abstract: The BCR-ABL gene rearrangement, the initial event in the development of chronic myeloid leukemia, primarily produces clonal expansion in CML by blocking apoptosis, a genetically programmed process of autonomous cell death. The mechanism by which BCR-ABL blocks apoptosis remains unclear, although recent data are beginning to shed light on the signaling pathway. As with other antiapoptotic signals, BCR-ABL induces cellular resistance to a wide spectrum of cytotoxic antitumor agents. However, apoptosis induced by both cytotoxic T lymphocytes and natural killer or lymphokine-activated killer cells is not blocked by BCR-ABL. A substantial number of patients with chronic myeloid leukemia can now be cured, and the prognosis has improved even for those patients who are not cured. Interferon-alpha has emerged as the treatment of choice for patients who do not undergo an allogeneic bone marrow transplantation. The availability of allogeneic bone marrow transplantation has been increased by the ability to find unrelated donors, although graft-versus-host disease remains a major problem. Adoptive immunotherapy with donor lymphocyte transfusions will induce durable remissions and possibly cures in many patients who relapse after allogeneic BMT. Moreover, a number of investigational approaches, especially autologous BMT, appear promising.
authors.affiliation: Johns Hopkins Oncology Center, Baltimore, MD 21287-8967, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Jones
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016026:Bone Marrow Transplantation; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016219:Immunotherapy, Adoptive; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology / Q000628:therapy; D017710:Lymphocyte Transfusion; D051379:Mice; D010677:Philadelphia Chromosome
chemical_list: D007155:Immunologic Factors; D016898:Interferon-alpha; D016044:Fusion Proteins, bcr-abl