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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2284-2290.
Prepublished online as a Blood First Edition Paper on November 26, 2003; DOI 10.1182/blood-2003-07-2575.
Submitted July 29, 2003
Accepted October 21, 2003
Molecular response to Imatinib in late chronic phase chronic myeloid leukemia
Gianantonio Rosti, Giovanni Martinelli, Simona Bassi, Marilina Amabile, Elena Trabacchi, Barbara Giannini, Daniela Cilloni, Barbara Izzo, Antonio de Vivo, Nicoletta Testoni, Giovanna Rege Cambrin, Francesca Bonifazi, Simona Soverini, Simona Luatti, Enrico Gottardi, Daniele Alberti, Fabrizio Pane, Francesco Salvatore, Giuseppe Saglio, and Michele Baccarani*
Institute of Hematology and Medical Oncology, 'L. and A. Seragnoli', University of Bologna, Bologna, Italy
Division of Hematology and Internal Medicine, Department of Clinical and Biological Science, University of Turin, Turin, Italy
CEINGE Biotecnologie Avanzate and Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, Naples, Italy
Novartis Pharma, Origgio, Italy
* Corresponding author; email: mbaccarani{at}med.unibo.it.
Imatinib is a tyrosine-kinase inhibitor which binds to ABL proteins and induces cytogenetic remissions in patients with chronic myeloid leukemia. In these patients measuring response by molecular techniques is clearly required. We determined the cytogenetic and molecular response (CgR, MR) to Imatinib in 191 previously Interferon- treated, late chronic phase, Ph+ CML patients. MR was assessed with Real-time quantitative (Taqman) RT-PCR and was expressed as the ratio between BCR/ABL and  2-microglobulin x 100, the lowest level of detectability of the method being 0.00001. A complete CgR (CCgR) was achieved in 85/191 cases (44%) and was maintained for 2 years in 67/85 cases (79%). A reduction of the transcript level of more than 2 logs was achieved in all but nine cases of CCgR vs none of 23 cases of partial CgR. In the CCgRs the median value of MR was 0.0008 after 12 months and 0.0001 after 24 months, the transcript level being undetectable in 22 cases. We conclude that in CCgRs the degree of MR may vary from 2 to more than 4 logs, and that there is a progressive decrease of transcript level by the time. Only one of 22 negative cases has relapsed as yet.
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|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Baccarani, G. Martinelli, G. Rosti, E. Trabacchi, N. Testoni, S. Bassi, M. Amabile, S. Soverini, F. Castagnetti, D. Cilloni, et al.
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104(13):
4245 - 4251.
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|
|
|
|
|
|
|
J. Cortes, S. O'Brien, and H. Kantarjian
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October 1, 2004;
104(7):
2204 - 2205.
[Full Text]
[PDF]
|
|
|
|
|
|
|
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October 1, 2004;
104(7):
1979 - 1988.
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|
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|
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