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: Michael S Mathisen, Susan O'Brien, Deborah Thomas, Jorge Cortes, Hagop Kantarjian, Farhad Ravandi
• Journal: Current hematologic malignancy reports (Curr Hematol Malig Rep) Vol. 6 Issue 3 Pg. 187-94 (Sep 2011) ISSN: 1558-822X [Electronic] United States
• PMID: 21660654 (Publication Type: Journal Article, Review)

Chemical References

• Benzamides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Thiazoles
• Imatinib Mesylate
• Protein-Tyrosine Kinases
• Fusion Proteins, bcr-abl
• Dasatinib

Topics

• Benzamides
• Clinical Trials as Topic
• Combined Modality Therapy
• Dasatinib
• Fusion Proteins, bcr-abl (antagonists & inhibitors, metabolism)
• Humans
• Imatinib Mesylate
• Philadelphia Chromosome
• Piperazines (therapeutic use)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)
• Protein Kinase Inhibitors (therapeutic use)
• Protein-Tyrosine Kinases (antagonists & inhibitors, metabolism)
• Pyrimidines (therapeutic use)
• Stem Cell Transplantation
• Thiazoles (therapeutic use)
• Transplantation, Homologous