Quantitative monitoring of the T315I mutation in patients with chronic myeloid leukemia (CML).
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.
Chomel
Jean-Claude
JC
Service d'Hématologie et Oncologie Biologique, CHU de Poitiers, France. j.c.chomel@chu-poitiers.fr
Sorel
Nathalie
N
Bonnet
Marie-Laure
ML
Bertrand
Angelina
A
Brizard
Françoise
F
Saulnier
Pierre-Jean
PJ
Roy
Lydia
L
Guilhot
François
F
Turhan
Ali G
AG
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
D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl