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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2926-2932.
Prepublished online as a Blood First Edition Paper on July 15, 2004; DOI 10.1182/blood-2004-03-1134.
Previous Article | Table of Contents | Next Article 
NEOPLASIA
Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations
Susan Branford,
Zbigniew Rudzki,
Ian Parkinson,
Andrew Grigg,
Kerry Taylor,
John F. Seymour,
Simon Durrant,
Peter Browett,
Anthony P. Schwarer,
Chris Arthur,
John Catalano,
Michael F. Leahy,
Robin Filshie,
Kenneth Bradstock,
Richard Herrmann,
David Joske,
Kevin Lynch, and
Tim Hughes
From the Institute of Medical and Veterinary Science, Adelaide, Australia; the Royal Melbourne Hospital, Melbourne, Australia; the Mater Hospital, Brisbane, Queensland, Australia; the Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; the Royal Brisbane Hospital, Brisbane, Australia; the Auckland Hospital, Auckland, New Zealand; The Alfred Hospital, Melbourne, Victoria, Australia; the Royal North Shore Hospital, Sydney, New South Wales, Australia; the Monash Medical Centre, Melbourne, Victoria, Australia; the Fremantle Hospital, Fremantle, Western Australia, Australia; the St Vincent's Hospital, Melbourne, Victoria, Australia; the Westmead Hospital, Sydney, New South Wales, Australia; the Royal Perth Hospital, Perth, Australia; the Sir Charles Gairdner Hospital, Perth, Western Australia, Australia; the Novartis Pharmaceuticals Australia, Sydney, Australia.
Mutations within the BCR-ABL kinase domain in imatinib-treated chronic myeloid leukemia (CML) are the main mechanism of acquired resistance. The early detection of mutations should provide clinical benefit by allowing early intervention. Quantitative polymerase chain reaction (RQ-PCR) results of BCR-ABL mRNA were correlated with mutation analysis in 214 patients treated with imatinib. We determined whether there was a difference in the incidence of mutations between the patients with a more than 2-fold rise in BCR-ABL and patients with stable or decreasing levels. Of the 56 patients with a more than 2-fold rise, 34 (61%) had detectable mutations (median rise, 3.0-fold; 25th-75th percentiles, 2.3-5.2). In 31 (91%) of these 34 patients, the mutation was present at the time of the rise and became detectable within 3 months in the remaining patients. Only 1 (0.6%) of 158 patients with stable or decreasing BCR-ABL levels had a detectable mutation, P less than .0001. Thus, a more than 2-fold rise identified 34 (97%) of 35 patients with a mutation. We conclude that a rise in BCR-ABL of more than 2-fold can be used as a primary indicator to test patients for BCR-ABL kinase domain mutations.

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|
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|

|
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 |
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|
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|
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|

|
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|
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|
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|
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|
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|
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|

|
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|
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|
 |
|

|
 |

|
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|
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|
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|
 |
|

|
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|
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July 1, 2006;
108(1):
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|
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January 1, 2006;
2006(1):
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|
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|

|
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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October 1, 2005;
65(19):
8912 - 8919.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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106(7):
2520 - 2526.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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106(6):
2128 - 2137.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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51(7):
1263 - 1266.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Chronic Myeloid Leukemia: Current Application of Cytogenetics and Molecular Testing for Diagnosis and Treatment
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March 1, 2005;
80(3):
390 - 402.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Chu, H. Xu, N. P. Shah, D. S. Snyder, S. J. Forman, C. L. Sawyers, and R. Bhatia
Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment
Blood,
March 1, 2005;
105(5):
2093 - 2098.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. L. Ilaria Jr.
Pathobiology of Lymphoid and Myeloid Blast Crisis and Management Issues
Hematology,
January 1, 2005;
2005(1):
188 - 194.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
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