Deborah L White
Affiliation: South Australia
- OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinibDeborah L White
Division of Hematology, Institute of Medical and Veterinary Science IMVS and Hanson Institute, Adelaide, South Australia
Blood 108:697-704. 2006..Determining interpatient and interdrug differences in cellular uptake and retention could allow individual optimization of kinase inhibitor therapy...
- Dasatinib cellular uptake and efflux in chronic myeloid leukemia cells: therapeutic implicationsDevendra K Hiwase
Division of Haematology, Institute of Medical and Veterinary Science, University of Adelaide, Adelaide, South Australia, Australia
Clin Cancer Res 14:3881-8. 2008..The relevance of OCT-1 activity and efflux pumps in determining intracellular uptake and retention (IUR) of dasatinib was assessed...
- Functional activity of the OCT-1 protein is predictive of long-term outcome in patients with chronic-phase chronic myeloid leukemia treated with imatinibDeborah L White
Haematology Department, Centre for Cancer Biology, SA Pathology IMVS Campus, University of Adelaide, Frome Road, Adelaide, Australia
J Clin Oncol 28:2761-7. 2010..We now report the impact of OA on loss of response, disease transformation, and survival after 5 years of imatinib...
- In vitro sensitivity to imatinib-induced inhibition of ABL kinase activity is predictive of molecular response in patients with de novo CMLDeborah White
Division of Haematology, Institute of Medical and Veterinary Science IMVS and Hanson Institute, Adelaide, Australia
Blood 106:2520-6. 2005..The IC50imatinib potentially provides a new prognostic indicator for molecular response in patients treated with imatinib...
- Predicting the response of CML patients to tyrosine kinase inhibitor therapyDeborah L White
Division of Haematology, SA Pathology IMVS RAH Campus, Frome Road, Adelaide, South Australia, Australia
Curr Hematol Malig Rep 4:59-65. 2009..In the future, assays that directly assess the efficacy of the protein-drug interaction, taking into account factors intrinsic to the patient and the amount of drug freely available in the plasma, are likely to be of greater value...
- Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activityDeborah L White
Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, Australia
Blood 110:4064-72. 2007..This pretherapy assay identifies patients at greatest risk of suboptimal response where dose intensity is critical, and those likely to respond equally well to standard dose imatinib...
- Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockade and predict response in chronic myeloid leukemiaDeborah White
Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, Australia
J Clin Oncol 25:4445-51. 2007..This suggests that patient-tailored dosing may be more rational than a fixed dose for all. Dose optimization potentially could be based on accurate measurement of the level of BCR-ABL kinase inhibition achieved in vivo...
- Degree of kinase inhibition achieved in vitro by imatinib and nilotinib is decreased by high levels of ABCB1 but not ABCG2Laura N Eadie
Division of Hematology, SA Pathology, Adelaide, South Australia, Australia
Leuk Lymphoma 54:569-78. 2013..Imatinib and nilotinib appear to be transported by ABCB1 but do not interact strongly with ABCG2. Furthermore, ABCB1 efflux of nilotinib may be concentration-dependent with transport occurring at clinically relevant concentrations...
- Tyrosine kinase inhibitor resistance in chronic myeloid leukemia cell lines: investigating resistance pathwaysCarine Tang
Department of Haematology, SA Pathology, Adelaide, Australia
Leuk Lymphoma 52:2139-47. 2011..This suggests that currently available TKIs share the same susceptibilities to drug resistance...
- The poor response to imatinib observed in CML patients with low OCT-1 activity is not attributable to lower uptake of imatinib into their CD34+ cellsJane R Engler
Division of Haematology, SA Pathology RAH Campus, Adelaide, Australia
Blood 116:2776-8. 2010..Therefore kinase inhibition in these mature cells, and not the CD34(+) cells, may be the key determinant of response in CML...
- Chronic phase chronic myeloid leukemia patients with low OCT-1 activity randomized to high-dose imatinib achieve better responses and have lower failure rates than those randomized to standard-dose imatinibDeborah L White
Department of Haematology, SA Pathology, RAH Campus, Adelaide, Australia
Haematologica 97:907-14. 2012....
- Impact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg/day of imatinib as initial therapyTimothy P Hughes
Institute of Medical and Veterinary Science, Adelaide, Australia
Blood 112:3965-73. 2008..Superior responses achieved in patients able to tolerate imatinib at 600 mg suggests that early dose intensity may be critical to optimize response in CP-CML. The trial was registered at www.ANZCTR.org.au as #ACTRN12607000614493...
- Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER studyDavid M Ross
Haematology, SA Pathology, Adelaide, Australia
Blood 122:515-22. 2013..These results confirm the safety and efficacy of a trial of imatinib withdrawal in stable UMRD with frequent, sensitive molecular monitoring and early rescue of molecular relapse. ..
- Optimizing the selection of kinase inhibitors for chronic myeloid leukemia patientsDevendra K Hiwase
Hematology Division, SA Pathology, Adelaide, SA 5000, Australia
Expert Rev Hematol 4:285-99. 2011..In addition, we provide commentary on the therapeutic options for patients who fail imatinib therapy...
- Predicting the response of CML patients to tyrosine kinase inhibitor therapyDeborah L White
Haematology Department, SA Pathology RAH Site, Frome Road, Adelaide, South Australia
Curr Hematol Malig Rep 6:88-95. 2011....
- CML patients with deep molecular responses to TKI have restored immune effectors, decreased PD-1 and immune suppressorsAmy Hughes
Department of Haematology, SA Pathology, Adelaide, SA, Australia
Blood . 2017..Maximal restoration of immune responses occurred only in MR4.5, as demonstrated by increased NK cell and effector T cell cytolytic function, reduced T cell PD-1 expression and reduced numbers of Monocytic-MDSC...
- KIR2DL5B genotype predicts outcomes in CML patients treated with response-directed sequential imatinib/nilotinib strategyDavid T Yeung
Department of Genetics and Molecular Pathology, Centre for Cancer Biology, and Department of Haematology, SA Pathology, Adelaide, SA, Australia School of Medicine and
Blood 126:2720-3. 2015..KIR genotyping may add valuable prognostic information to future baseline predictive scoring systems in CP-CML patients and facilitate optimal frontline treatment selection. ..
- Is telomerase a player in chronic phase chronic myeloid leukemia, disease progression and imatinib resistance?Deborah L White
Division of Haematology, IMVS and Hanson Institute, Adelaide, Australia
Leuk Lymphoma 49:1022-3. 2008
- OCT-1 function varies with cell lineage but is not influenced by BCR-ABLJane R Engler
Department of Haematology, SA Pathology RAH Campus, Frome Road, Adelaide Australia
Haematologica 96:213-20. 2011..The present study examined whether cell lineage and BCR-ABL expression influenced OCT-1 activity...
- TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targetsDavid T Yeung
Department of Haematology, and Department of Genetics and Molecular Pathology and Centre for Cancer Biology, SA Pathology, Adelaide, Australia Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia Australasian Leukemia and Lymphoma Group, Melbourne, Australia
Blood 125:915-23. 2015..This trial supports the feasibility and efficacy of an imatinib-based approach with selective, early switching to nilotinib. This trial was registered at www.anzctr.org.au as #12607000325404. ..
- ABCB1 Overexpression Is a Key Initiator of Resistance to Tyrosine Kinase Inhibitors in CML Cell LinesLaura N Eadie
Cancer Theme, South Australian Health and Medical Research Institute SAHMRI, Adelaide, South Australia
PLoS ONE 11:e0161470. 2016..This provides a rationale for investigating this phenomenon in patients undergoing TKI therapy. ..
- CYP2C8 Genotype Significantly Alters Imatinib Metabolism in Chronic Myeloid Leukaemia PatientsDaniel T Barratt
Discipline of Pharmacology, Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia
Clin Pharmacokinet . 2016..The aims of this study were to determine the effects of the CYP2C8*3 and *4 polymorphisms on imatinib metabolism and plasma imatinib concentrations in chronic myeloid leukaemia (CML) patients...
- Monoclonal antibody targeting of IL-3 receptor α with CSL362 effectively depletes CML progenitor and stem cellsEva Nievergall
Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
Blood 123:1218-28. 2014..Thus, our data support the further evaluation of CSL362 therapy in CML. ..
- Imatinib increases the intracellular concentration of nilotinib, which may explain the observed synergy between these drugsDeborah L White
Blood 109:3609-10. 2007