Constant BCR-ABL transcript level >or=0.1% (IS) in patients with CML responding to imatinib with complete cytogenetic remission may indicate mutation analysis.
OBJECTIVE
Of 140 chronic myeloid leukemia patients responding to imatinib with complete cytogenetic remission, 32 exhibited a plateau of BCR-ABL values at >or=0.1% level in a minimum of three subsequent samples (minimal duration, 6 - 9 months). Median follow-up of unchanged BCR-ABL transcript level was 12 months (range, 6 - 64). We tested this group of patient for BCR-ABL mutations to reveal resistance development and to evaluate the risk of disease progression.


METHODS
Altogether, 134 samples of peripheral blood of these 32 patients were tested for mutation in BCR-ABL kinase domain.


RESULTS
Mutation was detected by direct sequencing in 9 of 32 patients (28%). Loss of complete cytogenetic remission or 1 log rise of BCR-ABL was observed in five of nine patients at a median of 5 months (range, 4-17) since first detection of mutation. One patient with no mutation relapsed 12 months after the start of the BCR-ABL plateau. In 5 of 32 patients without mutation (16%), BCR-ABL level significantly decreased after the first plateau to levels that stayed unchanged for a median of 11 months (range, 7-28).


CONCLUSIONS
We show here that the BCR-ABL constant levels >or=0.1% (BCR-ABL plateau) in imatinib-responding patients may indicate mutation analysis. This approach highly reduces the number of examinations for mutation in chronic myeloid leukemia responders and may present cost-effective alternative applicable in clinical practice.
Poláková
Katerina Machová
KM
Institute of Hematology and Blood Transfusion, Department of Molecular Genetics, Prague, Czech Republic. katerina.machova@uhkt.cz
Polívková
Václava
V
Rulcová
Jana
J
Klamová
Hana
H
Jurcek
Tomás
T
Dvoráková
Dana
D
Zácková
Daniela
D
Pospísil
Zdenek
Z
Mayer
Jirí
J
Moravcová
Jana
J
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D020732:Cytogenetic Analysis; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics*; D012074:Remission Induction; D015203:Reproducibility of Results
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl