title: Role of tyrosine kinase inhibitors in the management of Philadelphia chromosome-positive acute lymphoblastic leukemia.
abstract: The Philadelphia chromosome is the most common cytogenetic abnormality found in adult patients diagnosed with acute lymphoblastic leukemia. The result of this abnormality is the BCR-ABL protein, a constitutively active kinase involved in cell signaling and survival. When managed with multiagent chemotherapy regimens alone, patients have traditionally had an inferior outcome in terms of remission duration and overall survival when compared with patients who are Philadelphia chromosome-negative. Small-molecule tyrosine kinase inhibitors, such as imatinib and dasatinib, directly inhibit the BCR-ABL kinase, offering a targeted approach as a therapeutic option. As a result of several clinical trials with adequate follow-up, imatinib combined with chemotherapy represents the current standard of care for patients with newly diagnosed disease. Allogeneic stem cell transplantation has previously been the only modality to offer the potential for a cure, and it still should be considered for all patients deemed able to tolerate such an intervention. Second-generation tyrosine kinase inhibitors, such as dasatinib, may further improve the outcome in these patients. The role of molecular monitoring and the use of tyrosine kinase inhibitors after stem cell transplantation are areas of active investigation, and the results of ongoing trials will help to clarify the optimal management of these patients.
authors.affiliation: Department of Leukemia, The University of Texas-M D Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Mathisen
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D001549:Benzamides; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D000069439:Dasatinib; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D013844:Thiazoles / Q000627:therapeutic use; D014184:Transplantation, Homologous
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib