Innovations in the management of leukemia: role of biologic therapies.
Chronic myelogenous leukemia (CML) results from clonal proliferation of malignant hematologic progenitor cells and is responsible for 7% to 15% of all adult leukemias. The hallmark of CML is a genetic translocation between chromosomes 9 and 22 (the Philadelphia chromosome), which creates the abnormal bcr-abl gene and a continuously activated Bcr-Abl protein. Bcr-Abl tyrosine kinase activity leads to signal transduction and cell growth. Traditional therapies for CML include allogeneic stem cell transplantation, interferon alfa, and oral chemotherapeutic agents. However, because Bcr-Abl is the causative abnormality in CML, it represents an ideal target for rational biologic therapy. Imatinib mesylate is an orally available tyrosine kinase inhibitor that specifically blocks Bcr-Abl function. Clinical trials have demonstrated that imatinib mesylate produces rapid responses in patients with all stages of CML, including those who were resistant to interferon alfa therapy or intolerant of it. When imatinib mesylate therapy was initiated early in the course of CML, there was a complete hematologic response in 98% of the patients and a complete cytogenetic response in 72% of the patients. Although long-term safety and survival data are not yet available, imatinib mesylate is a promising new treatment option for CML that targets the molecular cause of the disease.
Duffy
Kathleen M
KM
University of Pennsylvania Medical Center, Philadelphia, Pa, USA.
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D006801:Humans; D000068877:Imatinib Mesylate; D007938:Leukemia / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases