[Monitoring of minimal residual disease in patients with chronic myeloleukemia: clinical value of real-time polymerase chain reaction].
OBJECTIVE
To quantitatively determine minimal residual disease (MRD) by real-time polymerase chain reaction (PCR) in patients with a chronic phase (CP) of chronic myeloid leukemia (CML).


METHODS
A molecular response was analyzed in 53 CML CP patients with incomplete and complete cptogenetic response (ICR and CCR) during imatinib therapy (median follow-up 36 months). BCR-ABL gene type p210 expression was quantitatively determined by real-time PCR under the TaqMan technology (an ICycler IQ device). The beta2 microglobulin (beta2M) gene was used as a reference gene. The results were expressed as the ratio: the number of BCR-ABL copies to that of beta2M x 10(5), as well as the difference of the common logarithm (lg) of the baseline expression level (BEL) and the result obtained: CEL lg-result lg.


RESULTS
The study revealed a correlation of the results of real-time PCR with those of cytogenetic analysis and showed it possible to study not only bone marrow, but also peripheral blood. Some negative real-time PCR results were checked using more sensitive PCR techniques. MRD was identified in most CML patients showing ICR and CCR during imatinib therapy. The reduction in BCR-ABL transcript levels by less than 2 lg (as compared to BEL) was associated with a cytogenetic recurrence and that by less than 3 lg was associated with a permanent high cytogenetic response. In patients with a cytogenetic recurrence, the median of BCR-ABL transcript levels was higher than that in patients with a permanent stable or unstable cytogenetic response. An elevation of BCR-ABL transcript levels over time antedated the development of a cytogenetic recurrence.


CONCLUSIONS
Quantitative monitoring by real-time PCR gives additional information on the dynamics of MRD in CML patients treated with glivec and permits improvement of study protocols for patients with CML at complete clinicohematological and cytogenetic remission.
Chelysheva
E Iu
EIu
Turkina
A G
AG
Misiurin
A V
AV
Aksenova
E V
EV
Domracheva
E V
EV
Zakharova
A V
AV
Khoroshko
N D
ND
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000097:blood / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D016313:Genes, abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D018365:Neoplasm, Residual; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D001613:beta 2-Microglobulin / Q000097:blood / Q000235:genetics*
D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D001613:beta 2-Microglobulin; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl