Michael W N Deininger

Summary

Affiliation: Oregon Health and Science University
Country: USA

Publications

  1. doi request reprint Nilotinib
    Michael W Deininger
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, L592, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA
    Clin Cancer Res 14:4027-31. 2008
  2. ncbi request reprint The effect of prior exposure to imatinib on transplant-related mortality
    Michael Deininger
    Center for Hematologic Malignancies, Oregon Health and Science University, Portland, OR 97239, USA
    Haematologica 91:452-9. 2006
  3. ncbi request reprint Basic science going clinical: molecularly targeted therapy of chronic myelogenous leukemia
    Michael W N Deininger
    BMT Leukemia Center, Oregon Health and Science University, 3181 SW Sam Jackson Park Road L592, Portland 97239, USA
    J Cancer Res Clin Oncol 130:59-72. 2004
  4. ncbi request reprint Resistance and relapse with imatinib in CML: causes and consequences
    Michael Deininger
    Oregon Health and Science University, Portland, Oregon 97239, USA
    J Natl Compr Canc Netw 6:S11-S21. 2008
  5. ncbi request reprint Optimizing therapy of chronic myeloid leukemia
    Michael W N Deininger
    Oregon Health and Science University, Cancer Institute, Portland, OR 97239, USA
    Exp Hematol 35:144-54. 2007
  6. ncbi request reprint Specific targeted therapy of chronic myelogenous leukemia with imatinib
    Michael W N Deininger
    BMT Leukemia Center, Oregon Health and Science University, Mailcode L592, 3181 S W Sam Jackson Park Road, Portland, OR 97239, USA
    Pharmacol Rev 55:401-23. 2003
  7. ncbi request reprint The development of imatinib as a therapeutic agent for chronic myeloid leukemia
    Michael Deininger
    Oregon Health and Science University Cancer Institute, 3181 SW Sam Jackson Park Rd, Mailcode L592, Portland, OR 97239, USA
    Blood 105:2640-53. 2005
  8. ncbi request reprint The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome-negative cells
    Michael W N Deininger
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, Portland, Oregon 97239, USA
    Cancer 110:1509-19. 2007
  9. ncbi request reprint Resistance to imatinib: mechanisms and management
    Michael Deininger
    OHSU Cancer Institute, Center for Hematologic Malignancies, Portland, OR 97239, USA
    J Natl Compr Canc Netw 3:757-68. 2005
  10. ncbi request reprint Combined Abl inhibitor therapy for minimizing drug resistance in chronic myeloid leukemia: Src/Abl inhibitors are compatible with imatinib
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University, Portland 97239, USA
    Clin Cancer Res 11:6987-93. 2005

Research Grants

  1. Biology of Imatinib-Resistant Mutants of BCR-ABL
    Michael Deininger; Fiscal Year: 2006
  2. Biology of Imatinib-Resistant Mutants of BCR-ABL
    Michael Deininger; Fiscal Year: 2007
  3. Biology of Imatinib-Resistant Mutants of BCR-ABL
    Michael Deininger; Fiscal Year: 2009

Detail Information

Publications77

  1. doi request reprint Nilotinib
    Michael W Deininger
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, L592, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA
    Clin Cancer Res 14:4027-31. 2008
  2. ncbi request reprint The effect of prior exposure to imatinib on transplant-related mortality
    Michael Deininger
    Center for Hematologic Malignancies, Oregon Health and Science University, Portland, OR 97239, USA
    Haematologica 91:452-9. 2006
    ..Such patients may be eligible for allogeneic stem cell transplantation (SCT), raising the question whether imatinib therapy may compromise the outcome of subsequent SCT...
  3. ncbi request reprint Basic science going clinical: molecularly targeted therapy of chronic myelogenous leukemia
    Michael W N Deininger
    BMT Leukemia Center, Oregon Health and Science University, 3181 SW Sam Jackson Park Road L592, Portland 97239, USA
    J Cancer Res Clin Oncol 130:59-72. 2004
    ..Last, the question will be addressed, why imatinib is so successful, and whether its success might be reproducible in other malignant conditions...
  4. ncbi request reprint Resistance and relapse with imatinib in CML: causes and consequences
    Michael Deininger
    Oregon Health and Science University, Portland, Oregon 97239, USA
    J Natl Compr Canc Netw 6:S11-S21. 2008
    ..Given the wealth of publications on the subject, including all information was not feasible and choices had to be made...
  5. ncbi request reprint Optimizing therapy of chronic myeloid leukemia
    Michael W N Deininger
    Oregon Health and Science University, Cancer Institute, Portland, OR 97239, USA
    Exp Hematol 35:144-54. 2007
    ..Lastly, resistance to imatinib and the potential of second-generation Abl kinase inhibitors in the setting of clinical resistance are considered...
  6. ncbi request reprint Specific targeted therapy of chronic myelogenous leukemia with imatinib
    Michael W N Deininger
    BMT Leukemia Center, Oregon Health and Science University, Mailcode L592, 3181 S W Sam Jackson Park Road, Portland, OR 97239, USA
    Pharmacol Rev 55:401-23. 2003
    ..Perspectives for further development are also discussed...
  7. ncbi request reprint The development of imatinib as a therapeutic agent for chronic myeloid leukemia
    Michael Deininger
    Oregon Health and Science University Cancer Institute, 3181 SW Sam Jackson Park Rd, Mailcode L592, Portland, OR 97239, USA
    Blood 105:2640-53. 2005
    ..In this manuscript, we review the preclinical and clinical development of imatinib for the therapy of CML, resistance and strategies that may help to eliminate resistant or residual leukemia...
  8. ncbi request reprint The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome-negative cells
    Michael W N Deininger
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, Portland, Oregon 97239, USA
    Cancer 110:1509-19. 2007
    ..In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells...
  9. ncbi request reprint Resistance to imatinib: mechanisms and management
    Michael Deininger
    OHSU Cancer Institute, Center for Hematologic Malignancies, Portland, OR 97239, USA
    J Natl Compr Canc Netw 3:757-68. 2005
    ..Understanding the mechanisms underlying disease persistence will be crucial for developing strategies to eradicate residual leukemia...
  10. ncbi request reprint Combined Abl inhibitor therapy for minimizing drug resistance in chronic myeloid leukemia: Src/Abl inhibitors are compatible with imatinib
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University, Portland 97239, USA
    Clin Cancer Res 11:6987-93. 2005
    ..As combination therapy is frequently used to prevent emergence of resistance, the combination of imatinib with an inhibitor of imatinib-resistant Bcr-Abl mutants (e.g., Src/Abl inhibitors AP23848 and BMS-354825) was investigated...
  11. ncbi request reprint Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies
    Marcus M Schittenhelm
    Department of Medicine, Division of Hematology Oncology, Oregon Health and Science University, Portland, USA
    Cancer Res 66:473-81. 2006
    ..Our studies suggest that dasatinib may have clinical efficacy against human neoplasms that are associated with gain-of-function KIT mutations...
  12. ncbi request reprint Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
    Brian J Druker
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    N Engl J Med 355:2408-17. 2006
    ..Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy...
  13. ncbi request reprint In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland 97239, USA
    Cancer Res 65:4500-5. 2005
    ..Thus, both inhibitors hold promise for treating imatinib-refractory CML...
  14. pmc Determining the rise in BCR-ABL RNA that optimally predicts a kinase domain mutation in patients with chronic myeloid leukemia on imatinib
    Richard D Press
    Department of Pathology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97201, USA
    Blood 114:2598-605. 2009
    ..We conclude that the currently recommended 10-fold threshold to trigger mutation screening is insensitive and not universally applicable...
  15. ncbi request reprint Sensitivity of oncogenic KIT mutants to the kinase inhibitors MLN518 and PD180970
    Amie S Corbin
    Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Blood 104:3754-7. 2004
    ..As phase 1 clinical trials of MLN518 in AML have shown little toxicity, our data suggest MLN518 is a promising candidate for the treatment of SM or AML with KIT mutations...
  16. ncbi request reprint Characterization of murine JAK2V617F-positive myeloproliferative disease
    Thomas G P Bumm
    Center for Hematologic Malignancies, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Cancer Res 66:11156-65. 2006
    ..The disease was not transplantable and prolonged observation showed normalization of blood counts in most JAK2(V617F) mice, suggesting that the mutation may not confer self-renewal capacity...
  17. pmc The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCR-ABLT315I and exhibits a narrow resistance profile
    Christopher A Eide
    Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA
    Cancer Res 71:3189-95. 2011
    ..Taken together, these findings support continued evaluation of DCC-2036 as an important new agent for treatment-refractory CML...
  18. pmc AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Cancer Cell 16:401-12. 2009
    ..Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML...
  19. ncbi request reprint SRCircumventing imatinib resistance
    Michael W N Deininger
    Oregon Health and Science University Cancer Institute, Center for Hematologic Malignancies, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Cancer Cell 6:108-10. 2004
    ..These studies demonstrate the importance and impact of conducting scientific studies as part of clinical trials...
  20. doi request reprint Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, Oregon, USA
    Clin Cancer Res 17:212-21. 2011
    ....
  21. ncbi request reprint Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571)
    Paul La Rosée
    Oregon Health and Sciences University Cancer Institute, Division of Hematology and Medical Oncology, Portland, Oregon 97239, USA
    Cancer Res 62:7149-53. 2002
    ....
  22. ncbi request reprint Activating alleles of JAK3 in acute megakaryoblastic leukemia
    Denise K Walters
    Howard Hughes Medical Institute, Portland, Oregon 97239, USA
    Cancer Cell 10:65-75. 2006
    ..These findings illustrate the biological importance of gain-of-function JAK3 mutations in leukemogenesis and demonstrate the utility of proteomic approaches to identifying clinically relevant mutations...
  23. pmc An intron-derived insertion/truncation mutation in the BCR-ABL kinase domain in chronic myeloid leukemia patients undergoing kinase inhibitor therapy
    Jennifer Laudadio
    Department of Pathology, Oregon Health and Science University, Portland, OR, USA
    J Mol Diagn 10:177-80. 2008
    ..These findings demonstrate that kinase domain insertions are an alternative (and not entirely uncommon) mutational mechanism in CML patients undergoing kinase inhibitor therapy...
  24. pmc High-throughput sequencing screen reveals novel, transforming RAS mutations in myeloid leukemia patients
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Blood 113:1749-55. 2009
    ....
  25. ncbi request reprint Antileukemic activity of lysophosphatidic acid acyltransferase-beta inhibitor CT32228 in chronic myelogenous leukemia sensitive and resistant to imatinib
    Paul La Rosée
    Division of Hematology and Medical Oncology, Oregon Health and Sciences University, Portland, Oregon
    Clin Cancer Res 12:6540-6. 2006
    ..Inhibition of LPAAT-beta induces growth arrest and apoptosis in cancer cell lines, implicating LPAAT-beta as a potential drug target in neoplasia...
  26. ncbi request reprint Practical management of patients with chronic myeloid leukemia receiving imatinib
    Michael W N Deininger
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    J Clin Oncol 21:1637-47. 2003
    ..The treatment recommendations are intended to optimize therapy with imatinib while taking into account a patient's specific circumstances...
  27. ncbi request reprint AMN107: tightening the grip of imatinib
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland, Oregon, 97239, USA
    Cancer Cell 7:117-9. 2005
    ..The implications of these results, and the potential role this and other novel ABL inhibitors may have in treating patients with CML, are discussed...
  28. ncbi request reprint A half-log increase in BCR-ABL RNA predicts a higher risk of relapse in patients with chronic myeloid leukemia with an imatinib-induced complete cytogenetic response
    Richard D Press
    Department of Pathology, Center for Hematologic Malignancies, Cancer Institute, and Howard Hughes Medical Institute, Oregon Health and Science University, Portland, Oregon 97201, USA
    Clin Cancer Res 13:6136-43. 2007
    ..Although CCR is usually durable, a minority of patients relapse. Biomarkers capable of predicting those CCR patients with a higher risk of relapse would improve therapeutic management...
  29. pmc Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations
    Heather A Bradeen
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 108:2332-8. 2006
    ..However, sequencing uniformly revealed T315I, consistent with the need for a T315I inhibitor, to completely block resistance...
  30. ncbi request reprint Coexistence of phosphotyrosine-dependent and -independent interactions between Cbl and Bcr-Abl
    Isabelle Gaston
    Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Ore 97239, USA
    Exp Hematol 32:113-21. 2004
    ..Following this initial interaction, Cbl can then become tyrosine phosphorylated and interact with the SH2 domain of Bcr-Abl, further stabilizing the complex...
  31. pmc Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib
    Ian J Griswold
    Center for Hematologic Malignancies, Oregon Health and Science University, 3181 S W Sam Jackson Park Rd, Portland, OR 97239 3098, USA
    Mol Cell Biol 26:6082-93. 2006
    ..The drug resistance and transformation potency of mutants may determine the outcome of patients on therapy with Abl kinase inhibitors...
  32. ncbi request reprint Several Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib
    Amie S Corbin
    Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Blood 101:4611-4. 2003
    ..This study highlights the need for biochemical and biologic characterization, before a resistant phenotype can be ascribed to a mutant...
  33. pmc SGX393 inhibits the CML mutant Bcr-AblT315I and preempts in vitro resistance when combined with nilotinib or dasatinib
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Proc Natl Acad Sci U S A 105:5507-12. 2008
    ..These findings suggest that combination of a T315I inhibitor with the current clinically used inhibitors may be useful for reduction of Bcr-Abl mutants in Philadelphia chromosome-positive leukemia...
  34. ncbi request reprint In vitro efficacy of combined treatment depends on the underlying mechanism of resistance in imatinib-resistant Bcr-Abl-positive cell lines
    Paul La Rosée
    Oregon Health and Science University Cancer Institute, Division of Hematology and Medical Oncology, Portland, OR 97239, USA
    Blood 103:208-15. 2004
    ..These data underline the importance of resistance testing and provide a rational approach for dose-adjusted administration of imatinib when combined with other agents...
  35. ncbi request reprint New Bcr-Abl inhibitors in chronic myeloid leukemia: keeping resistance in check
    Thomas O'Hare
    Oregon Health and Science University Cancer Institute, Howard Hughes Medical Institute, Portland, Oregon 97239, USA
    Expert Opin Investig Drugs 17:865-78. 2008
    ..Improved Abl inhibitor therapies will be useful in achieving maximum disease control but a clinical T315I inhibitor remains a high priority...
  36. ncbi request reprint In vitro and in vivo activity of ATP-based kinase inhibitors AP23464 and AP23848 against activation-loop mutants of Kit
    Amie S Corbin
    Oregon Health and Science University, Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 106:227-34. 2005
    ..Thus, AP23464 and AP23848 potently and selectively target activation-loop mutants of Kit in vitro and in vivo and could have therapeutic potential against D816V-expressing malignancies...
  37. pmc A gene expression signature of CD34+ cells to predict major cytogenetic response in chronic-phase chronic myeloid leukemia patients treated with imatinib
    Shannon K McWeeney
    Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Blood 115:315-25. 2010
    ..Our classifier may allow directing more aggressive therapy upfront to the patients most likely to benefit while sparing good-risk patients from unnecessary toxicity...
  38. ncbi request reprint Bcr-Abl kinase domain mutations and the unsettled problem of Bcr-AblT315I: looking into the future of controlling drug resistance in chronic myeloid leukemia
    Christopher A Eide
    Center for Hematologic Malignancies, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Clin Lymphoma Myeloma 7:S120-30. 2007
    ..We also critically assess the role of combined Abl kinase inhibitor therapy in overcoming resistance and provide recommendations for monitoring patients for kinase domain mutations...
  39. pmc BCR-ABL SH3-SH2 domain mutations in chronic myeloid leukemia patients on imatinib
    Daniel W Sherbenou
    Cell and Developmental Biology, Oregon Health and Science University, Portland, OR, USA
    Blood 116:3278-85. 2010
    ..Regulatory domain mutations are uncommon but may explain resistance in some patients without mutations in the kinase domain...
  40. ncbi request reprint In chronic myeloid leukemia white cells from cytogenetic responders and non-responders to imatinib have very similar gene expression signatures
    Lucy C Crossman
    Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Haematologica 90:459-64. 2005
    ..However, a subgroup of patients is refractory at the cytogenetic level. Clinically, it would be advantageous to identify such patients a priori, since they may benefit from more aggressive therapy...
  41. ncbi request reprint Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis
    Ian J Griswold
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland 97239, USA
    Blood 104:2912-8. 2004
    ..In analogy to imatinib mesylate in BCR-ABL-positive acute leukemia, MLN518-induced remissions may not be durable. Our studies provide the basis for integrating this compound into chemotherapy and transplantation protocols...
  42. ncbi request reprint Can we afford to let sleeping dogs lie?
    Michael W N Deininger
    Oregon Health and Science University, USA
    Blood 105:1840-1. 2005
    ..In this issue of Blood, Chu and colleagues report several patients with KD mutations at the time of complete cytogenetic response (CCR), implicating mutations as a cause of disease persistence...
  43. ncbi request reprint RNAi-induced down-regulation of FLT3 expression in AML cell lines increases sensitivity to MLN518
    Denise K Walters
    Department of Hematology and Oncology, Howard Hughes Medical Institute, Oregon Health and Science University, and Portland Veterans Affairs VA Medical Center, 3181 Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 105:2952-4. 2005
    ..Furthermore, siRNA-induced down-regulation of FLT3 increased the sensitivity of both cell lines to treatment with the FLT3 inhibitor MLN518. This illustrates the potential benefit of combined therapeutic approaches...
  44. ncbi request reprint Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 104:2532-9. 2004
    ..The potency of AP23464 against imatinib mesylate-refractory Bcr-Abl and its distinct binding mode relative to imatinib mesylate warrant further investigation of AP23464 for the treatment of CML...
  45. pmc A BCR-ABL mutant lacking direct binding sites for the GRB2, CBL and CRKL adapter proteins fails to induce leukemia in mice
    Kara J Johnson
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, Oregon, United States of America
    PLoS ONE 4:e7439. 2009
    ..Our data suggest that inhibition of BCR-ABL-induced leukemia by disrupting protein interactions could be possible, but would require blocking of multiple sites...
  46. pmc Acute dasatinib exposure commits Bcr-Abl-dependent cells to apoptosis
    Jennifer L Snead
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Blood 114:3459-63. 2009
    ..Furthermore, they challenge the widely held notion that continuous target inhibition is required for optimal efficacy of kinase inhibitors...
  47. doi request reprint Management of drug toxicities in chronic myeloid leukaemia
    Michael J Mauro
    Knight Cancer Institute, Center for Hematologic Malignancies, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, UHN 73C, Portland, OR 97239, USA
    Best Pract Res Clin Haematol 22:409-29. 2009
    ..This article reviews the toxicities related to the currently available ABL inhibitors - their basis, relevance and management...
  48. pmc MET receptor sequence variants R970C and T992I lack transforming capacity
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, Oregon 97239, USA
    Cancer Res 70:6233-7. 2010
    ....
  49. ncbi request reprint Phosphoproteomic analysis of AML cell lines identifies leukemic oncogenes
    Denise K Walters
    Department of Hematology and Oncology, Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, 3181 Sam Jackson Park Road, and Portland VA Medical Center, Portland, OR 97239, USA
    Leuk Res 30:1097-104. 2006
    ..This study illustrates the benefit of LC-MS/MS mass spectrometry and siRNA for the identification of novel targets and mutations...
  50. pmc BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML
    Richard D Press
    Department of Pathology, Oregon Health and Science University, Portland, OR 97201, USA
    Blood 107:4250-6. 2006
    ..1; 95% CI, 3.1-22; P < .001). The achievement of either a 2-log molecular response at the time of CCR or a 3-log response anytime thereafter is a significant and independent prognostic marker of subsequent progression-free survival...
  51. ncbi request reprint Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions
    Brian J P Huntly
    Bone Marrow Transplantation Leukemia, Oregon Health and Science University, Portland, OR
    Blood 102:2205-12. 2003
    ..04), for major cytogenetic response (P =.008) in chronic phase, and for hematologic response in advanced phases (P =.007) of CML. This finding suggests that differences in survival may become apparent with longer follow-up...
  52. ncbi request reprint Cytogenetic studies in patients on imatinib
    Michael W N Deininger
    Bone Marrow Transplant Leukemia Center, Oregon Health and Sciences University, Portland, OR 97239, USA
    Semin Hematol 40:50-5. 2003
    ..This is a novel phenomenon whose causality and prognostic implications require thorough and systematic evaluation...
  53. pmc CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms
    Jeffrey W Tyner
    Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA
    Blood 115:5232-40. 2010
    ....
  54. ncbi request reprint High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy
    Stephanie G Willis
    OHSU Cancer Institute, 3181 SW Sam Jackson Park Rd, Mailcode L592, Portland, OR 97239, USA
    Blood 106:2128-37. 2005
    ..KD mutants present at low levels do not invariably lead to relapse, and additional factors are required to induce a fully drug-resistant phenotype...
  55. doi request reprint How much and how long: tyrosine kinase inhibitor therapy in chronic myeloid leukemia
    Elie Traer
    Oregon Health and Science University Knight Cancer Institute, Portland, OR, USA
    Clin Lymphoma Myeloma Leuk 10:S20-6. 2010
    ..More than 10 years after the introduction of imatinib, optimization of TKI therapy for CML continues...
  56. pmc RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, Portland, USA
    Blood 111:2238-45. 2008
    ..This technique, with additional development, might eventually offer the potential to match specific therapies with individual patients based on a functional assay...
  57. pmc RNAi screen for rapid therapeutic target identification in leukemia patients
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Proc Natl Acad Sci U S A 106:8695-700. 2009
    ..Combination of this technique with whole-genome sequencing will represent an ideal tool for oncogenic target identification such that specific therapies can be matched with individual patients...
  58. pmc Absence of SKP2 expression attenuates BCR-ABL-induced myeloproliferative disease
    Anupriya Agarwal
    Division of Hematology and Oncology, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Blood 112:1960-70. 2008
    ..Hence, stabilization of p27 by inhibiting its recognition by SCF(SKP2) may be therapeutically useful...
  59. doi request reprint New strategies for the first-line treatment of chronic myeloid leukemia: can resistance be avoided?
    Jennifer L Snead
    Oregon Health and Science University Cancer Institute, Portland, OR, USA
    Clin Lymphoma Myeloma 8:S107-17. 2008
    ..Herein, we review current and emerging paradigms for using Abl kinase inhibitors to achieve maximal disease control and strategies to eradicate disease by targeting leukemic stem cells...
  60. ncbi request reprint Establishment of a murine model of aggressive systemic mastocytosis/mast cell leukemia
    Shadmehr Demehri
    Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Exp Hematol 34:284-8. 2006
    ..This easy and inexpensive tumor model should be useful for testing potential drugs with activity against KIT(D816V)...
  61. pmc High-throughput sequence analysis of the tyrosine kinome in acute myeloid leukemia
    Marc M Loriaux
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Blood 111:4788-96. 2008
    ....
  62. ncbi request reprint Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study
    Charles L Sawyers
    Department of Medicine and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
    Blood 99:3530-9. 2002
    ..Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs...
  63. ncbi request reprint High levels of BAX, low levels of MRP-1, and high platelets are independent predictors of response to imatinib in myeloid blast crisis of CML
    Thoralf Lange
    Department of Hematology, University of Leipzig, Germany
    Blood 101:2152-5. 2003
    ..Combined into a score, these parameters may be clinically useful for risk-adapted patient stratification...
  64. ncbi request reprint Imatinib normalizes bone marrow vascularity in patients with chronic myeloid leukemia in first chronic phase
    Mathias Rumpel
    Blood 101:4641-3. 2003
  65. ncbi request reprint Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study
    Moshe Talpaz
    M D Anderson Cancer Center, Houston, Texas, USA
    Blood 99:1928-37. 2002
    ..Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity...
  66. ncbi request reprint BCR-ABL kinase domain mutations in chronic myeloid leukemia: not quite enough to cause resistance to imatinib therapy?
    Thoralf Lange
    Department of Hematology Oncology, University of Leipzig, Germany
    Cell Cycle 4:1761-6. 2005
    ..Unexpectedly, kinase domain mutant clones were not invariably selected in the presence of drug, suggesting that additional mechanisms must contribute to a fully drug resistant leukemia...
  67. ncbi request reprint Emergence of clonal cytogenetic abnormalities in Ph- cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority
    Thomas Bumm
    Department of Hematology, University of Leipzig, Germany
    Blood 101:1941-9. 2003
    ..They indicate that patients on imatinib should be followed with conventional cytogenetics, even after induction of CCR...
  68. ncbi request reprint Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia
    Christopher A Eide
    Howard Hughes Medical Institute, Chevy Chase, MD, USA
    Blood 110:2242-9. 2007
    ..Last, we assess the potential of Abl kinase inhibitor combinations to induce stable responses even in advanced CML and interpret the emerging data in the context of CML pathogenesis...
  69. ncbi request reprint hOCT 1 and resistance to imatinib
    Lucy C Crossman
    Blood 106:1133-4; author reply 1134. 2005
  70. ncbi request reprint Quantitative reverse transcription polymerase chain reaction should not replace conventional cytogenetics for monitoring patients with chronic myeloid leukemia during early phase of imatinib therapy
    Thoralf Lange
    Department of Hematology, University of Leipzig, Germany
    Haematologica 89:49-57. 2004
    ..In this study, we compared qPCR and conventional cytogenetics for monitoring of patients during the early phases of imatinib therapy...
  71. ncbi request reprint Residual disease in chronic myeloid leukemia after induction of molecular remission
    Thoralf Lange
    N Engl J Med 349:1483-4. 2003
  72. ncbi request reprint Imatinib in patients with newly diagnosed chronic-phase chronic myeloid leukemia
    Stephen G O'Brien
    School of Clinical and Laboratory Sciences, The Medical School, University of Newcastle, Newcastle, UK
    Semin Hematol 40:26-30. 2003
    ..Overall survival was not different in the two groups at 19 months, reflecting efficient rescue of IFN/LDAC failures with imatinib. Imatinib should now be considered the standard therapy for newly diagnosed patients with CML...
  73. ncbi request reprint Chronic myeloid leukemia in 2006: a perspective
    Michael J Mauro
    Haematologica 91:152. 2006
  74. pmc The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia
    Ross L Levine
    Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 106:3377-9. 2005
    ..These data indicate that the JAK2V617F allele is present in acute and chronic myeloid malignancies but not in lymphoid malignancies...
  75. ncbi request reprint The BCR/ABL-extra signal fluorescence in situ hybridization system reliably detects deletions upstream of the ABL locus: implications for reporting of results and followup of chronic myelogenous leukemia patients
    Christel Müller
    Cancer Genet Cytogenet 136:149-50. 2002
  76. ncbi request reprint Biology of chronic myelogenous leukemia--signaling pathways of initiation and transformation
    Junia V Melo
    Department of Haematology, Imperial College, London and Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    Hematol Oncol Clin North Am 18:545-68, vii-viii. 2004
    ..CML is subject to an inexorable progression from an "indolent" chronic phase to a terminal blast crisis. Disease progression is presumed to be associated with the phenomenon of genomic instability...
  77. ncbi request reprint c-CBL is not required for leukemia induction by Bcr-Abl in mice
    Daniela M Dinulescu
    Department of Cell and Developmental Biology, OR, USA
    Oncogene 22:8852-60. 2003
    ..Most importantly, in a transplantation model of CML, Bcr-Abl was capable of inducing fatal leukemia in mice in the absence of c-Cbl protein. Our results indicate that c-Cbl is dispensable for Bcr-Abl-induced leukemogenesis in mice...

Research Grants5

  1. Biology of Imatinib-Resistant Mutants of BCR-ABL
    Michael Deininger; Fiscal Year: 2006
    ..Such crucial proteins may then be exploited as drug targets for the treatment of chronic myeloid leukemia, and further, for other types of cancer. ..
  2. Biology of Imatinib-Resistant Mutants of BCR-ABL
    Michael Deininger; Fiscal Year: 2007
    ..Such crucial proteins may then be exploited as drug targets for the treatment of chronic myeloid leukemia, and further, for other types of cancer. ..
  3. Biology of Imatinib-Resistant Mutants of BCR-ABL
    Michael Deininger; Fiscal Year: 2009
    ..Such crucial proteins may then be exploited as drug targets for the treatment of chronic myeloid leukemia, and further, for other types of cancer. ..