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The basic model. Our mathematical model is based on the architecture of the hematopoi-etic system as proposed by Irving Weissman and colleagues 1,2. Denote by x 0 , x 1 , x 2 , and x 3 the abundances of normal hematopoietic stem cells, progenitors, differentiated cells, and terminally differentiated cells. Their respective leukemic abundances are given by y(More)
The clinical success of the ABL tyrosine kinase inhibitor imatinib in chronic myeloid leukaemia (CML) serves as a model for molecularly targeted therapy of cancer, but at least two critical questions remain. Can imatinib eradicate leukaemic stem cells? What are the dynamics of relapse due to imatinib resistance, which is caused by mutations in the ABL(More)
MOTIVATION With the advent of relatively affordable high-throughput technologies, DNA sequencing of cancers is now common practice in cancer research projects and will be increasingly used in clinical practice to inform diagnosis and treatment. Somatic (cancer-only) single nucleotide variants (SNVs) are the simplest class of mutation, yet their(More)
BACKGROUND BCR-ABL1 mutation analysis is recommended for chronic myeloid leukaemia patients. However, mutations may become undetectable after changing therapy, and it is unknown whether they have been eradicated. METHODS We examined longitudinal data of patients with imatinib-resistant mutations, which became undetectable by Sanger sequencing to determine(More)
Treatment with the tyrosine kinase inhibitor imatinib is the standard of care for newly diagnosed patients with chronic myeloid leukemia. In recent years, several second-generation inhibitors - such as dasatinib and nilotinib - have become available: these promise to overcome some of the mutations associated with acquired resistance to imatinib. Despite(More)
UNLABELLED The standard method used by high-throughput genome sequencing facilities for detecting mislabelled samples is to use independently generated high-density SNP data to determine sample identity. However, as it has now become commonplace to have multiple samples sequenced from the same source, such as for analysis of somatic variants using matched(More)
BACKGROUND Detection and quantitation of BCR-ABL1 transcripts are crucial for managing patients with chronic myeloid leukemia (CML). Although real-time quantitative polymerase chain reaction (RT-qPCR) can be measured on an International Scale (IS), this has not become fully universal. By using a WHO international standard panel established for calibrating(More)
An automated cartridge-based detection system (GeneXpert; Cepheid) is being widely adopted in low throughput laboratories for monitoring BCR-ABL1 transcript in chronic myelogenous leukaemia. This Australian study evaluated the longitudinal performance specific characteristics of the automated system.The automated cartridge-based system was compared(More)
We evaluated BCR-ABL1 kinetics in patients treated with nilotinib and analyzed whether a dynamic model of changes in BCR-ABL1 levels over time could be used to predict long-term responses. Patients from the nilotinib registration trial (CAMN107A2101; registered at http://www.clinicaltrials.gov as NCT00109707 ) who had imatinib-resistant or -intolerant(More)
Accurate and standardized methods for the quantitative measurement of BCR-ABL1 are a prerequisite for monitoring of treatment response in t(9;22)-positive leukemia. Here, we describe a novel multiplex assay system based on the proven TaqMan and Armored RNA technologies and optimized for sensitive detection of three BCR-ABL1 fusion transcripts and ABL1 in a(More)