title: Recent advances in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.
abstract: The advent of imatinib, a selective inhibitor of the ABL tyrosine kinase, has revolutionized the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Combined with chemotherapy, imatinib exerts remarkable efficacy in patients with newly diagnosed disease with a complete remission (CR) rate of 95% and a survival rate of 55% at 3 years. Profound eradication of leukemia cells not only provides patients with a better chance for receiving allogeneic hematopoietic stem cell transplantation during first CR but also contributes to durable CR even without transplantation. Despite such improvement, however, relapse does occur, mainly owing to acquisition of resistance. Growing comprehension of the molecular mechanisms of resistance to imatinib has led to the development of novel BCR-ABL inhibitors that yield higher affinity for BCR-ABL and/or potent inhibitory activity against other target molecules such as SRC family kinases. The second-generation ABL kinase inhibitors, namely dasatinib and nilotinib, are already showing clinical activity in patients with imatinib-resistant Ph+ ALL, and other novel agents are undergoing preclinical and early clinical evaluation. Further improvement in treatment results will be achieved by identifying each patient's disease profile based on information obtained before and during treatment and by optimizing subsequent treatment accordingly.
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-8550, Japan. myanada@mte.biglobe.ne.jp.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Yanada
authors.affiliation: Aichi Cancer Center, Nagoya, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ohno
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D003131:Combined Modality Therapy / Q000639:trends; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012074:Remission Induction / Q000379:methods
chemical_list: D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl