Quantitative monitoring of BCR/ABL transcript during STI-571 therapy.
PCR for the BCR/ABL fusion transcript provides a highly sensitive and specific method for detecting minimal residual disease in patients with chronic myeloid leukemia (CML). We sought to determine if quantitative PCR measurement of peripheral blood BCR/ABL transcript can be used to monitor response in CML patients with clinically evident disease while receiving the protein tyrosine kinase inhibitor STI-571. Serial bone marrow cytogenetics and peripheral blood BCR/ABL mRNA levels were measured in 17 patients [9 with chronic phase (CP) and 8 with accelerated phase or blast crisis (AP/BC)] during 1 year of treatment. Overall, quantitative PCR BCR/ABL transcript level decreased by a median of 0.9 log during the first 3 months, and by 1.6 logs by 12 months. Among cytogenetic responders (6 CP and 2 AP/BC), median BCR/ABL copy number was 0.9 and 2.1 logs lower than baseline after 3 and 12 months of treatment, respectively. No patient became PCR-negative for BCR/ABL. Among cytogenetic non-responders, BCR/ABL transcript level decreased by 0.4 logs after 3 months, with no subsequent reductions. At study entry, BCR/ABL expression in cytogenetic responders and non-responders was similar. However, BCR/ABL expression became significantly different 3 months after treatment (p = 0.02), and increasingly different with continued therapy (p = 0.04, 0.005, 0.0008 at 6, 9 and 12 months, respectively). Our results demonstrate that PBMC BCR/ABL mRNA levels correlate well with response to STI-571. This non-invasive, rapid and sensitive PCR-based assay can be used to monitor response to STI-571.
Wu
Catherine J
CJ
Center for Hematologic Oncology, Department of Biostatistics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Neuberg
Donna
D
Chillemi
Antoinette
A
McLaughlin
Stephen
S
Hochberg
Ephraim P
EP
Galinsky
Ilene
I
DeAngelo
Daniel
D
Soiffer
Robert J
RJ
Alyea
Edwin P
EP
Capdeville
Renaud
R
Stone
Richard M
RM
Ritz
Jerome
J
D000328:Adult; D000368:Aged; D001549:Benzamides; D001856:Bone Marrow Examination; D020732:Cytogenetic Analysis; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis* / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology*; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000592:standards; D012680:Sensitivity and Specificity
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl