title: Quantitative monitoring of the T315I mutation in patients with chronic myeloid leukemia (CML).
abstract: Tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of chronic myeloid leukemia (CML). However, resistances are occasionally observed, mainly due to mutations within the BCR-ABL kinase domain. The T315I substitution confers complete resistance to TKIs commonly used in clinical practice. In the present study, we used an allele-specific quantitative-RT-PCR to perform a molecular follow-up of BCR-ABL transcripts harboring the T315I mutation. We retrospectively quantified BCR-ABL315I mRNA in five patients who acquired the T315I mutation. Our results highlight the relevance of allele-specific Q-RT-PCR experiments for the monitoring of mutated BCR-ABL transcripts and suggest that the kinetics of emergence of T315I mutant mRNA is influenced by the stage of the disease and the presence of previous BCR-ABL kinase domain mutations.
authors.affiliation: Service d'Hématologie et Oncologie Biologique, CHU de Poitiers, France. j.c.chomel@chu-poitiers.fr
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Chomel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sorel
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Bonnet
authors.forename: Angelina
authors.initials: A
authors.lastname: Bertrand
authors.forename: Françoise
authors.initials: F
authors.lastname: Brizard
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Saulnier
authors.forename: Lydia
authors.initials: L
authors.lastname: Roy
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.forename: Ali G
authors.initials: AG
authors.lastname: Turhan
mesh_terms: D000328:Adult; D000368:Aged; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl