Monitoring minimal residual disease and controlling drug resistance in chronic myeloid leukaemia patients in treatment with imatinib as a guide to clinical management.
Imatinib mesylate, binding to the inactive conformation of Bcr-Abl tyrosine kinase and suppressing the Ph chromosome positive clone, has revolutionized the treatment of chronic myeloid leukaemia (CML) patients. Given the high rates of clinical and cytogenetic remission achieved, the molecular monitoring of BCR-ABL transcript levels by RT-qPCR has become always more important to assess minimal residual disease. Recently, recommendations for harmonizing current methodologies for detecting and measuring BCR-ABL transcripts in CML patients have been suggested. Studies of imatinib-treated patients have determined that the BCR-ABL levels measured early in therapy may predict durable cytogenetic remission and in turn prolonged progression free-survival or acquisition of resistance. The major mechanism of imatinib resistance is clonal expansion of leukaemia cells with mutations in the Bcr-Abl fusion tyrosine kinase. The early reduction of such mutations may allow timely treatment intervention to prevent or overcome resistance. We review current trends in the management of chronic myeloid leukaemia patients undergoing treatment with tyrosine kinase inhibitors.
Martinelli
Giovanni
G
Institute of Hematology and Medical Oncology Seragnoli, University of Bologna, Bologna, Italy. gmartino@kaiser.alma.unibo.it
Iacobucci
Ilaria
I
Soverini
Simona
S
Cilloni
Daniela
D
Saglio
Giuseppe
G
Pane
Fabrizio
F
Baccarani
Michele
M
D001549:Benzamides; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D017408:Guidelines as Topic; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D008991:Monitoring, Physiologic / Q000379:methods; D009154:Mutation / Q000187:drug effects; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl