Chronic myeloid leukemia 2011: Successes, challenges, and strategies—Proceedings of the 5th annual BCR‐ABL1 positive and BCR‐ABL1 negative myeloproliferative neoplasms workshop

Mughal, Tariq I.; Radich, Jerald P.; Etten, Richard A. Van; Quintás‐Cardama, Alfonso; Skórski, Tomasz; Ravandi, Farhad; DeAngelo, Daniel J.; Gambacorti‐Passerini, Carlo; Martinelli, Giovanni; Tefferi, Ayalew

doi:10.1002/ajh.22097

Cited by 6 publications

(4 citation statements)

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“…However, some of them such as high resolution melt curve (HRM) analysis are progressively entering the general market and may have more wide application in the future. Allele specific (ASO) PCR based genotyping technique [9, 24, 38, 42, 48, 78–82,84,87]. This yechnique is widely used by some investigators but may be laborious and its increased sensitivity would identify mutations at extremely low level (<1% or even lower) the clinical significance of which is yet to be established. High Resolution Melt Curve Analysis (HRM) [83, 84].…”

Section: Other Less Frequently Used Techniquesmentioning

confidence: 99%

“…Allele specific (ASO) PCR based genotyping technique [9, 24, 38, 42, 48, 78–82,84,87]. This yechnique is widely used by some investigators but may be laborious and its increased sensitivity would identify mutations at extremely low level (<1% or even lower) the clinical significance of which is yet to be established.…”

Section: Other Less Frequently Used Techniquesmentioning

confidence: 99%

“…It is not yet established whether the mutated clones predate treatment with TKI (as a result of genomic instability) [44–46] and then gain a growth advantage with treatment, on a similar model to antibiotic resistance [9, 47–52] or whether they develop de novo during TKI therapy [13].…”

Section: Introductionmentioning

confidence: 99%

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BCR‐ABL1 kinase domain mutations: Methodology and clinical evaluation

et al. 2012

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The introduction of tyrosine kinase inhibitors (TKIs), starting with imatinib and followed by second and third generation TKIs, has significantly changed the clinical management of patients with chronic myeloid leukemia (CML). Despite their unprecedented clinical success, a proportion of patients fail to achieve complete cytogenetic remission by 12 months of treatment (primary resistance) while others experience progressive resistance after an initial response (secondary resistance). BCR‐ABL1 kinase domain (KD) mutations have been detected in a proportion of patients at the time of treatment failure, and therefore their identification and monitoring plays an important role in therapeutic decisions particularly when switching TKIs. When monitoring KD mutations in a clinical laboratory, the choice of method should take into account turnaround time, cost, sensitivity, specificity, and ability to accurately quantify the size of the mutant clone. In this article, we describe in a “manual” style the methods most widely used in our laboratory to monitor KD mutations in patients with CML including direct sequencing, D‐HPLC, and pyrosequencing. Advantages, disadvantages, interpretation of results, and their clinical applications are reviewed for each method. Am. J. Hematol., 2012. © 2011 Wiley Periodicals, Inc.

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Section: Other Less Frequently Used Techniquesmentioning

confidence: 99%

Section: Other Less Frequently Used Techniquesmentioning

confidence: 99%

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BCR‐ABL1 kinase domain mutations: Methodology and clinical evaluation

et al. 2012

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“…3 In the case of chronic myeloid leukemia, 3 kinase inhibitors have been approved for use (imatinib, dasatinib, and nilotinib, with others in development), and they have literally revolutionized the treatment of the disease, leading to prolonged remissions in the majority of patients. 4 The identification of these drugs that target BCR-Abl and other drugs that target a very wide range of other mutated or overexpressed kinases driving other cancers has become the primary focus of drug development for many pharmaceutical companies. Further fostering development is the relative ease of getting these drugs to market compared, for example, to novel drugs for treating heart failure.…”

Section: Article See P 2128mentioning

confidence: 99%

Double-Edged Sword of the New Cancer Therapeutics

Force

2012

Circulation

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Chronic Myeloid Leukaemia

Mughal

Goldman

2013

Encyclopedia of Life Sciences

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Chronic myeloid leukaemia (CML) is a clonal BCR–ABL1‐positive myeloproliferative disorder that results from an acquired genetic change in a single pluripotential haematopoietic stem cell. Although CML is rare, the lessons learned from unravelling its molecular biology over the past three decades have resulted in successful treatment for patients and also in a major paradigm shift in cancer medicine in general. Today many forms of cancer are being treated with drugs that target various molecular abnormalities known to play a role in the pathogenesis of the candidate disease. For CML patients, the introduction of the original tyrosine kinase inhibitor (TKI), imatinib mesylate, in 1998 was an important therapeutic milestone with most patients achieving a complete cytogenetic response and prolongation of survival compared with the previous therapies other than allogeneic stem cell transplantation (allo‐SCT). A small minority of patients were also able to achieve a complete molecular remission (CMR). With the more recent introduction of the second generation TKIs, dasatinib and nilotinib, the treatment results for the newly diagnosed patient in chronic phase (CP) seem even better, in particular the number of patients achieving CMR. Allo‐SCT is increasingly being offered when patients fail at least two lines of TKIs, except for children, where some specialists feel, it is appropriate to offer SCT as first or second line therapy. Efforts are also made to assess the potential for immunotherapy and other novel drugs, such as ponatinib, targeting specific subgroups of patients, for example, those with a mutant T315I clone have been developed. Key Concepts: Concept of targeted therapy in cancer medicine. Molecular pathogenesis of CML in CP: a single pathogenetic abnormality. Imatinib as a paradigm for successful molecularly targeted therapy. Second and third generation tyrosine kinase inhibitors: successes and challenges. Role of allogeneic stem transplantation in the era of the second generation TKI.

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Chronic myeloid leukemia 2011: Successes, challenges, and strategies—Proceedings of the 5th annual BCR‐ABL1 positive and BCR‐ABL1 negative myeloproliferative neoplasms workshop

Cited by 6 publications

References 128 publications

BCR‐ABL1 kinase domain mutations: Methodology and clinical evaluation

BCR‐ABL1 kinase domain mutations: Methodology and clinical evaluation

Double-Edged Sword of the New Cancer Therapeutics

Chronic Myeloid Leukaemia

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