James Griffin

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi BCR/ABL induces multiple abnormalities of cytoskeletal function
    R Salgia
    Division of Hematologic Malignancies, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 100:46-57. 1997
  2. ncbi The adapter protein Crkl links Cbl to C3G after integrin ligation and enhances cell migration
    N Uemura
    Department of Adult Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 274:37525-32. 1999
  3. ncbi Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion
    J Chen
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Br J Cancer 102:351-60. 2010
  4. ncbi Phosphatidyl inositol signaling by BCR/ABL: opportunities for drug development
    J D Griffin
    Leukemia Program, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Chemother Pharmacol 48:S11-6. 2001
  5. ncbi Role of FLT3 in leukemia
    D Gary Gilliland
    Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA
    Curr Opin Hematol 9:274-81. 2002
  6. ncbi Resistance to targeted therapy in leukaemia
    James D Griffin
    Leukemia Program, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Lancet 359:458-9. 2002
  7. ncbi ARG tyrosine kinase activity is inhibited by STI571
    K Okuda
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 97:2440-8. 2001
  8. ncbi Mechanisms of transformation by the BCR/ABL oncogene
    M Sattler
    Department of Adult Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Int J Hematol 73:278-91. 2001
  9. ncbi p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl
    R Salgia
    Division of Hematologic Malignacies, Dana Farber Cancer Institute, Boston, MA 02115
    Exp Hematol 24:310-3. 1996
  10. ncbi p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene
    R Salgia
    Division of Hematologic Malignancies, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 271:25198-203. 1996

Research Grants

  1. Regulation of Hematopoiesis by Notch Receptors
    James Griffin; Fiscal Year: 2006
  2. Regulation of Hematopoiesis by Notch Receptors
    James Griffin; Fiscal Year: 2003
  3. SURFACE ANTIGENS OF HUMAN MYELOID PROGENITOR CELLS
    James Griffin; Fiscal Year: 1993
  4. Regulation of Hematopoiesis by Notch Receptors
    James Griffin; Fiscal Year: 2007

Detail Information

Publications103 found, 100 shown here

  1. ncbi BCR/ABL induces multiple abnormalities of cytoskeletal function
    R Salgia
    Division of Hematologic Malignancies, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 100:46-57. 1997
    ..The increase in spontaneous motility and other defects of cytoskeletal function described here will be useful biological markers of the functional effects of BCR/ABL in hematopoietic cells...
  2. ncbi The adapter protein Crkl links Cbl to C3G after integrin ligation and enhances cell migration
    N Uemura
    Department of Adult Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 274:37525-32. 1999
    ..These data suggest that Crkl is involved in signaling pathways that regulate migration, possibly through a complex with Cbl and C3G...
  3. ncbi Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion
    J Chen
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Br J Cancer 102:351-60. 2010
    ..However, the events that lead to increased Notch activity during EMT of breast cancer cells are unknown...
  4. ncbi Phosphatidyl inositol signaling by BCR/ABL: opportunities for drug development
    J D Griffin
    Leukemia Program, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Chemother Pharmacol 48:S11-6. 2001
    ..As a result of these more detailed biochemical analyses of BCR/ABL function, new targets for future drug development have been identified...
  5. ncbi Role of FLT3 in leukemia
    D Gary Gilliland
    Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA
    Curr Opin Hematol 9:274-81. 2002
    ..Collectively, these data indicate that FLT3 may be a viable therapeutic target for treatment of AML...
  6. ncbi Resistance to targeted therapy in leukaemia
    James D Griffin
    Leukemia Program, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Lancet 359:458-9. 2002
  7. ncbi ARG tyrosine kinase activity is inhibited by STI571
    K Okuda
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 97:2440-8. 2001
    ..These results indicate that ARG is a target of the small molecule, tyrosine kinase inhibitor STI571...
  8. ncbi Mechanisms of transformation by the BCR/ABL oncogene
    M Sattler
    Department of Adult Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Int J Hematol 73:278-91. 2001
    ..This review will describe mechanisms of transformation by the BCR/ABL oncogene and opportunities for clinical intervention with specific signal transduction inhibitors such as STI-571 in CML...
  9. ncbi p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl
    R Salgia
    Division of Hematologic Malignacies, Dana Farber Cancer Institute, Boston, MA 02115
    Exp Hematol 24:310-3. 1996
    ..The binding of p120c-Cbl to the focal adhesion protein paxillin could contribute to the known adhesive defects of CML cells...
  10. ncbi p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene
    R Salgia
    Division of Hematologic Malignancies, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 271:25198-203. 1996
    ..These alterations in the structure of signaling proteins in focal adhesion like structures could contribute to the known adhesion abnormalities in CML cells...
  11. ncbi Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells
    S N Manie
    Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 272:4230-6. 1997
    ..These associations implicate HEF1 and Cas as important components in a cytoskeleton-linked signaling pathway initiated by ligation of beta1 integrin or BCR on human B cells...
  12. ncbi The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins
    N Uemura
    Division of Hematologic Malignancies, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Leukemia 11:376-85. 1997
    ..In BCR/ABL-transformed cells, CRKL but not CRK II, appears to form complexes which potentially link BCR/ABL, c-ABL, C3G, and SOS to the protooncoprotein, p120CBL...
  13. ncbi Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL)
    M Sattler
    Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    J Biol Chem 272:10248-53. 1997
    ..Such complexes could be important in propagating signals involving PI3K such as gene expression and adhesion...
  14. ncbi The BCR/ABL oncogene alters the chemotactic response to stromal-derived factor-1alpha
    R Salgia
    Department of Medical Oncology, Division of Hematologic Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Blood 94:4233-46. 1999
    ....
  15. ncbi BCR/ABL directly inhibits expression of SHIP, an SH2-containing polyinositol-5-phosphatase involved in the regulation of hematopoiesis
    M Sattler
    Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 19:7473-80. 1999
    ..Reexpression of SHIP in BCR/ABL-transformed Ba/F3 cells altered the biological behavior of cells in culture. The reduction of SHIP due to BCR/ABL is likely to directly contribute to the pathogenesis of CML...
  16. ncbi The BCR/ABL tyrosine kinase induces production of reactive oxygen species in hematopoietic cells
    M Sattler
    Dana Farber Cancer Institute, Department of Adult Oncology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 275:24273-8. 2000
    ..Further, treatment of MO7e cells with H(2)O(2) or pervanadate increased the tyrosine kinase activity of c-ABL. Drugs that alter ROS metabolism or reactivate PTPases may antagonize BCR/ABL transformation...
  17. ncbi Characterization of two SHP-2-associated binding proteins and potential substrates in hematopoietic cells
    H Gu
    Cancer Biology Program, Division of Hematology Oncology, Department of Medicine, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 272:16421-30. 1997
    ..Our results indicate that SHP-2 forms at least two separate complexes in hematopoietic cells and point to new potential SHP-2 targets...
  18. ncbi Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1)
    M Sattler
    Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    J Biol Chem 272:14320-6. 1997
    ..The shift in association of CRKL and its SH3-associated proteins from p120(CBL) to p110(HEF1) could contribute to different functional outcomes of "outside-in" integrin signaling in different cells...
  19. ncbi Histone deacetylase inhibitor NVP-LAQ824 has significant activity against myeloid leukemia cells in vitro and in vivo
    E Weisberg
    Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Leukemia 18:1951-63. 2004
    ..Taken together, these findings provide the framework for NVP-LAQ824 as a novel therapeutic in myeloid malignancies...
  20. ncbi SHIP1, an SH2 domain containing polyinositol-5-phosphatase, regulates migration through two critical tyrosine residues and forms a novel signaling complex with DOK1 and CRKL
    M Sattler
    Dana Farber Cancer Institute, Department of Adult Oncology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 276:2451-8. 2001
    ..Overall, these data suggest that proteins that interact with SHIP1 through Tyr(917) and Tyr(1020), such as DOK1 and SHC, are likely to be involved in the regulation of SHIP1 dependent migration...
  21. ncbi Smac mimetics: implications for enhancement of targeted therapies in leukemia
    E Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Leukemia 24:2100-9. 2010
    ..These results support the idea of using IAP inhibitors in conjunction with targeted tyrosine kinase inhibition to override drug resistance and suppress or eradicate residual disease...
  22. ncbi Drug resistance in mutant FLT3-positive AML
    E Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Oncogene 29:5120-34. 2010
    ....
  23. ncbi Role of the tyrosine phosphatase SHP-1 in K562 cell differentiation
    B Bruecher-Encke
    Department of Medicine, Beth Israel-Deaconess Medical Center, Boston, MA, USA
    Leukemia 15:1424-32. 2001
    ....
  24. ncbi Bcr/Abl expression stimulates integrin function in hematopoietic cell lines
    G Bazzoni
    Division of Tumor Virology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 98:521-8. 1996
    ..Consistent with these results, hematopoietic precursor cells from chronic myelogenous leukemia patients also showed increased adhesion to fibronectin...
  25. ncbi MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors
    L Wu
    Department of Adult Oncology, Dana Farber Cancer Institute and Departments of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Nat Genet 26:484-9. 2000
    ..These studies provide a molecular mechanism to explain the genetic links between mastermind and Notch in Drosophila and indicate that MAML1 functions as a transcriptional co-activator for NOTCH signalling...
  26. ncbi Mechanisms of resistance imatinib (STI571) in preclinical models and in leukemia patients
    E Weisberg
    Department of Adult Oncology, Dana-Farber Cancer Institute, and Departments of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
    Drug Resist Updat 4:22-8. 2001
    ..The available information on Glivec resistance will be reviewed...
  27. ncbi Tyrosine phosphorylation of Shc is not required for proliferation or viability signaling by granulocyte-macrophage colony-stimulating factor in hematopoietic cell lines
    M Durstin
    Department of Medicine, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Immunol 157:534-40. 1996
    ..These data indicate that the phosphorylation of Shc in response to GM-CSF is not required for proliferation or viability signaling in these cells...
  28. ncbi Regulation of surface expression of the granulocyte/macrophage colony-stimulating factor receptor in normal human myeloid cells
    S A Cannistra
    Division of Tumor Immunology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115
    Proc Natl Acad Sci U S A 87:93-7. 1990
    ..These data suggest that certain activators of neutrophil function may negatively regulate their biological effects by inducing down-regulation of the GM-CSF receptor...
  29. ncbi Signal transduction of the human granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors involves tyrosine phosphorylation of a common set of cytoplasmic proteins
    Y Kanakura
    Dana Farber Cancer Institute, Boston, MA 02115
    Blood 76:706-15. 1990
    ....
  30. ncbi Tyrosine phosphorylation of p95Vav in myeloid cells is regulated by GM-CSF, IL-3 and steel factor and is constitutively increased by p210BCR/ABL
    T Matsuguchi
    Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, MA 02115
    EMBO J 14:257-65. 1995
    ..A fusion protein consisting of glutathione-S-transferase and the SH2 domain of p95Vav (GST-Vav-SH2) precipitated JAK2, suggesting that this interaction is mediated by the SH2 domain of p95Vav.(ABSTRACT TRUNCATED AT 250 WORDS)..
  31. ncbi Granulocyte-macrophage colony-stimulating factor and other cytokines regulate surface expression of the leukocyte adhesion molecule-1 on human neutrophils, monocytes, and their precursors
    J D Griffin
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, MA 02115
    J Immunol 145:576-84. 1990
    ..These changes in adhesion proteins are likely to alter aggregation and mobility of both mature myeloid cells and their precursors in patients receiving certain types of cytokine therapy...
  32. ncbi AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL
    E Weisberg
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Br J Cancer 94:1765-9. 2006
    ....
  33. ncbi The cytokine-activated tyrosine kinase JAK2 activates Raf-1 in a p21ras-dependent manner
    K Xia
    Dana Farber Cancer Institute, Boston, MA, USA
    Proc Natl Acad Sci U S A 93:11681-6. 1996
    ..Taken together, these data suggest that JAK2 and p21ras cooperate to activate Raf-1...
  34. ncbi NOTCH1-induced T-cell leukemia in transgenic zebrafish
    J Chen
    Department of Medical Oncology, Dana Farber Cancer Institute of Harvard Medical School, Boston, MA 02115, USA
    Leukemia 21:462-71. 2007
    ..The ability of this model to detect a strong interaction between NOTCH1 and bcl2 suggests that genetic modifier screens have a high likelihood of revealing other genes that can cooperate with NOTCH1 to induce T-ALL...
  35. ncbi Signaling functions of the tyrosine residues in the betac chain of the granulocyte-macrophage colony-stimulating factor receptor
    K Okuda
    Division of Hematologic Malignancies, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 90:4759-66. 1997
    ..However, specific tyrosine residues are needed for activation of SHC and SHP2...
  36. ncbi Brain armadillo protein delta-catenin interacts with Abl tyrosine kinase and modulates cellular morphogenesis in response to growth factors
    Q Lu
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts, USA
    J Neurosci Res 67:618-24. 2002
    ..We suggest that delta-catenin is a possible Abl substrate and acts downstream of Abl to orchestrate actin-based cellular morphogenesis...
  37. ncbi Granulocyte colony-stimulating factor and its receptor
    G D Demetri
    Department of Medicine, Dana-Farber Cancer Institute, Boston, MA 02115
    Blood 78:2791-808. 1991
  38. ncbi Regulation of leukocyte adhesion molecule-1 (TQ1, Leu-8) expression and shedding by normal and malignant cells
    O Spertini
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, MA 02115
    Leukemia 5:300-8. 1991
    ..Thus, most CLL cells and some non-Hodgkin's lymphoma cells express a functionally active LAM-1 molecule which may correlate with their capacity to migrate through the circulation and disseminate into peripheral LN...
  39. ncbi The biology of GM-CSF: regulation of production and interaction with its receptor
    J D Griffin
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, Massachusetts 02115
    Int J Cell Cloning 8:35-44; discussion 44-5. 1990
    ..Signal transduction involves activation of a tyrosine kinase and possibly G protein-coupled stimulation of Na+/H+ exchange. The exact relationship of the two receptors needs further clarification...
  40. ncbi Differentiation-associated expression of two functionally distinct classes of granulocyte-macrophage colony-stimulating factor receptors by human myeloid cells
    S A Cannistra
    Division of Tumor Immunology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
    J Biol Chem 265:12656-63. 1990
    ..These data show that there are differentiation-associated differences in the regulation of the GM-CSF receptor which may have important physiological consequences...
  41. ncbi CD2 is involved in maintenance and reversal of human alloantigen-specific clonal anergy
    V A Boussiotis
    Dana Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115
    J Exp Med 180:1665-73. 1994
    ..These results suggest that in addition to blockade of B7 family members, inhibition of CD2 and, potentially, other costimulatory pathways that might reverse anergy will be necessary to maintain prolonged alloantigen-specific tolerance...
  42. ncbi Notch receptors and hematopoiesis
    S Kojika
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Exp Hematol 29:1041-52. 2001
    ..In this review, the details of Notch signaling will be discussed, with a focus on what is known about the role of Notch in hematopoiesis...
  43. ncbi Cloning and expression of a gamma-interferon-inducible gene in monocytes: a new member of a cytokine gene family
    H C Chang
    Laboratory of Immunobiology, Dana Farber Cancer Institute, Boston, MA 02115
    Int Immunol 1:388-97. 1989
    ..Protein sequence comparison reveals homology with other members of a recently described inducible cytokine family whose functions are yet to be defined...
  44. ncbi 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...
  45. ncbi FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in hematopoietic malignancies
    Jing Chen
    Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Oncogene 24:8259-67. 2005
    ..These data indicate that PKC412 may be a useful molecularly targeted therapy for MM associated with overexpression of FGFR3, and perhaps other diseases associated with dysregulation of FGFR3 or related mutants...
  46. ncbi Epidermal growth factor-independent transformation of Ba/F3 cells with cancer-derived epidermal growth factor receptor mutants induces gefitinib-sensitive cell cycle progression
    Jingrui Jiang
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Res 65:8968-74. 2005
    ..Our results provide a model system to study the function of mutated EGFR and the differential effects of pharmacologic EGFR inhibition on the distinct mutant forms of this tyrosine kinase...
  47. ncbi The small molecule tyrosine kinase inhibitor AMN107 inhibits TEL-PDGFRbeta and FIP1L1-PDGFRalpha in vitro and in vivo
    Elizabeth H Stover
    Division of Hematology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA
    Blood 106:3206-13. 2005
    ..In summary, AMN107 can inhibit myeloid proliferation driven by TEL-PDGFRbeta and FIP1L1-PDGFRalpha and may be a useful drug for treatment of patients with myeloproliferative disease who harbor these kinase fusions...
  48. ncbi Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL
    Hagop Kantarjian
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77230 1402, USA
    N Engl J Med 354:2542-51. 2006
    ..Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50...
  49. ncbi Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation
    Lizi Wu
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    EMBO J 24:2391-402. 2005
    ..This study has identified a novel, critical mechanism of transformation for an oncogene associated very specifically with salivary gland tumors, and identified potential targets for the development of novel therapies...
  50. ncbi Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis
    Ross L Levine
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Cell 7:387-97. 2005
    ..In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase...
  51. ncbi Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412
    Joseph D Growney
    Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    Blood 106:721-4. 2005
    ..These findings suggest that PKC412 may be a useful therapeutic agent for c-KIT-positive malignancies harboring the imatinib mesylate-resistant D816V or D816Y activation mutations...
  52. ncbi Identification of mTOR as a novel bifunctional target in chronic myeloid leukemia: dissection of growth-inhibitory and VEGF-suppressive effects of rapamycin in leukemic cells
    Matthias Mayerhofer
    Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Austria
    FASEB J 19:960-2. 2005
    ..In conclusion, rapamycin inhibits growth of CML cells in vitro and in vivo and, in addition, down-regulates expression of VEGF. Both effects may contribute to the antileukemic activity of the drug in CML...
  53. ncbi Interaction maps for kinase inhibitors
    James D Griffin
    Nat Biotechnol 23:308-9. 2005
  54. ncbi Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl
    Ellen Weisberg
    Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Cell 7:129-41. 2005
    ..AMN107 is a promising new inhibitor for the therapy of CML and Ph+ ALL...
  55. ncbi Activation of the PI3K/mTOR pathway by BCR-ABL contributes to increased production of reactive oxygen species
    Jeong H Kim
    Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 105:1717-23. 2005
    ..Finally, these results hint at novel targets for drug development that may aid traditional therapy...
  56. ncbi The Notch coactivator, MAML1, functions as a novel coactivator for MEF2C-mediated transcription and is required for normal myogenesis
    Huangxuan Shen
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 20:675-88. 2006
    ..Mechanistically, MAML1 appears to mediate cross-talk between Notch and MEF2 to influence myogenic differentiation...
  57. ncbi Activated Jak2 with the V617F point mutation promotes G1/S phase transition
    Christoph Walz
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    J Biol Chem 281:18177-83. 2006
    ....
  58. ncbi Stromal-mediated protection of tyrosine kinase inhibitor-treated BCR-ABL-expressing leukemia cells
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Mol Cancer Ther 7:1121-9. 2008
    ..This in vitro system helped to elucidate stromal-secreted viability factors that may play a role in stromal-mediated cytoprotection of tyrosine kinase inhibitor-treated leukemia cells...
  59. ncbi The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes
    Gerlinde Wernig
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Blood 111:3751-9. 2008
    ..Overall, our results suggest that constitutive activation of Jak2 requires an intact FERM domain for a transforming phenotype, and is necessary for activation of the major target of Jak2, STAT5...
  60. ncbi Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 111:3723-34. 2008
    ..Finally, BAG956 and rapamycin/RAD001 were shown to combine in a nonantagonistic fashion against BCR-ABL- and mutant FLT3-expressing cells both in vitro and in vivo...
  61. ncbi Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles
    Stefan Fröhling
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 12:501-13. 2007
    ....
  62. ncbi The transcriptional coactivator Maml1 is required for Notch2-mediated marginal zone B-cell development
    Lizi Wu
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Blood 110:3618-23. 2007
    ..Moreover, the number of MZB cells correlated with Maml1 gene dosage. Since all 3 Maml genes were expressed in MZB cells and their precursors, these results suggest that Maml1 is specifically required for Notch2 signaling in MZB cells...
  63. ncbi Potentiation of antileukemic therapies by Smac mimetic, LBW242: effects on mutant FLT3-expressing cells
    Ellen Weisberg
    Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Mol Cancer Ther 6:1951-61. 2007
    ..Finally, the combination of LBW242 and PKC412 was sufficient to override stromal-mediated viability signaling conferring resistance to PKC412...
  64. ncbi Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia
    Ellen Weisberg
    Dana Farber Cancer Institute, Mayer 540, 44 Binney Street, Boston, MA 02115, USA
    Nat Rev Cancer 7:345-56. 2007
    ..Here, we describe the mechanism of action of imatinib in CML, the structural basis of imatinib resistance, and the potential of second-generation BCR-ABL inhibitors to circumvent resistance...
  65. ncbi The notch regulator MAML1 interacts with p53 and functions as a coactivator
    Yongtong Zhao
    Division of Cancer Biology, Department of Medicine, ENH Research Institute, Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60201, USA
    J Biol Chem 282:11969-81. 2007
    ..elegans p53 homolog Cep-1. Thus, we present evidence for a novel coactivator function of MAML1 for p53, independent of its function as a coactivator of Notch signaling pathway...
  66. ncbi Identification of BCR-ABL point mutations conferring resistance to the Abl kinase inhibitor AMN107 (nilotinib) by a random mutagenesis study
    Arghya Ray
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Blood 109:5011-5. 2007
    ..Interestingly, most AMN107-resistant mutants were also resistant to imatinib mesylate. These results may predict some of the resistance mutations that will be detected in clinical trials with this kinase inhibitor...
  67. ncbi PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR
    Hongbing Zhang
    Department of Physiology, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People s Republic of China
    J Clin Invest 117:730-8. 2007
    ..In conclusion, PDGFR is a major target of negative feedback regulation in cells with activated mTOR, which limits the growth potential of TSC tumors...
  68. ncbi Effects of PKC412, nilotinib, and imatinib against GIST-associated PDGFRA mutants with differential imatinib sensitivity
    Ellen Weisberg
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Gastroenterology 131:1734-42. 2006
    ..In this study, we compare the effects of 3 tyrosine kinase inhibitors, PKC412 and nilotinib, and imatinib, on 2 GIST-related PDGFRA mutants, V561D and D842V, which possess differential sensitivity to imatinib...
  69. ncbi Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias
    Ellen Weisberg
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 109:2112-20. 2007
    ....
  70. ncbi AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, has in vitro activity against imatinib-resistant chronic myeloid leukemia
    Mirna Golemovic
    Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 11:4941-7. 2005
    ..These results strongly support investigation of the clinical efficacy of AMN107 in patients with CML...
  71. ncbi Prediction of resistance to small molecule FLT3 inhibitors: implications for molecularly targeted therapy of acute leukemia
    Jan Cools
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA, USA
    Cancer Res 64:6385-9. 2004
    ....
  72. ncbi Mutated tyrosine kinases as therapeutic targets in myeloid leukemias
    Martin Sattler
    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Adv Exp Med Biol 532:121-40. 2003
    ..FLT3 tyrosine kinase inhibitors are currently being evaluated in clinical trials and may be very useful therapeutic agents in AML...
  73. ncbi PKC412 overcomes resistance to imatinib in a murine model of FIP1L1-PDGFRalpha-induced myeloproliferative disease
    Jan Cools
    Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 3:459-69. 2003
    ..Our data establish PKC412 as molecularly targeted therapy for HES and other diseases expressing activated PDGFRalpha and demonstrate the potential of alternative kinase inhibitors to overcome resistance in target tyrosine kinases...
  74. ncbi A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome
    Jan Cools
    Brigham and Women s Hospital and Harvard Medical School, Boston, USA
    N Engl J Med 348:1201-14. 2003
    ..Recent reports of responses to imatinib in patients with the syndrome suggested that an activated kinase such as ABL, platelet-derived growth factor receptor (PDGFR), or KIT, all of which are inhibited by imatinib, might be the cause...
  75. ncbi Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification
    Scott A Armstrong
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 3:173-83. 2003
    ..Finally, we developed a mouse model of MLL and used bioluminescent imaging to determine that PKC412 is active against MLL in vivo...
  76. ncbi t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway
    Giovanni Tonon
    Genetics Branch, Center for Cancer Research, National Cancer Institute and the National Naval Medical Center, Bethesda, Maryland 20889, USA
    Nat Genet 33:208-13. 2003
    ..These data suggest a new mechanism to disrupt the function of a Notch co-activator in a common type of malignant salivary gland tumor...
  77. ncbi Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling
    Andrew P Weng
    Departments of Pathology, Brigham and Women s Hospital, Harvard Medical School Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Mol Cell Biol 23:655-64. 2003
    ....
  78. ncbi BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1alpha, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin
    Matthias Mayerhofer
    Department of Internal Medicine I, Division of Hematology and Hemostaseology, The University of Vienna, Austria
    Blood 100:3767-75. 2002
    ..Together, our data show that BCR/ABL induces VEGF- and HIF-1alpha gene expression through a pathway involving PI3-kinase and mTOR. BCR/ABL-induced VEGF expression may contribute to the pathogenesis and increased angiogenesis in CML...
  79. ncbi Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors
    Lizi Wu
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Mol Cell Biol 22:7688-700. 2002
    ..Thus, MAML proteins may modify Notch signaling in different cell types based on their own expression levels and differential activities and thereby contribute to the diversity of the biological effects resulting from Notch activation...
  80. ncbi The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment
    Boris Lin
    Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Res 62:5019-26. 2002
    ..The demonstrated anti-MM activity of PTK787, coupled with its antiangiogenic effects, provides the framework for clinical trials of this agent to overcome drug resistance and improve outcome in MM...
  81. ncbi The roles of FLT3 in hematopoiesis and leukemia
    D Gary Gilliland
    Brigham and Women s Hospital, Howard Hughes Medical Institute, Boston, MA, USA
    Blood 100:1532-42. 2002
    ..Taken together, these results suggest that FLT3 is an attractive therapeutic target for kinase inhibitors or other approaches for patients with mutations of this gene...
  82. ncbi Critical role for Gab2 in transformation by BCR/ABL
    Martin Sattler
    Dana Farber Cancer Institute, Department of Adult Oncology, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    Cancer Cell 1:479-92. 2002
    ..Our results identify Gab2 and its associated proteins as key determinants of the lineage and severity of BCR/ABL transformation...
  83. ncbi Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412
    Ellen Weisberg
    Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Cancer Cell 1:433-43. 2002
    ..PKC412 is a potent inhibitor of mutant FLT3 and is a candidate for testing as an antileukemia agent in AML patients with mutant FLT3 receptors...
  84. ncbi A fragment of paxillin binds the alpha 4 integrin cytoplasmic domain (tail) and selectively inhibits alpha 4-mediated cell migration
    Shouchun Liu
    Department of Vascular Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 277:20887-94. 2002
    ..Thus, paxillin binding to the alpha(4) tail leads to enhanced cell migration and inhibition of the alpha(4)-paxillin interaction selectively blocks the alpha4-dependent cellular responses...
  85. ncbi Differential expression and signaling of CBL and CBL-B in BCR/ABL transformed cells
    Martin Sattler
    Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Oncogene 21:1423-33. 2002
    ..These results demonstrate that BCR/ABL signals differentially through CBL and CBL-B, with downregulation of the CBL-B protein potentially contributing to BCR/ABL-mediated transformation...
  86. ncbi c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions
    Patrick C Ma
    Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Res 63:6272-81. 2003
    ..It would now be useful to study the inhibition of c-MET as a therapeutic target against SCLC...
  87. ncbi The EOL-1 cell line as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia
    Jan Cools
    Division of Hematology and the Howard Hughes Medical Institute, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 103:2802-5. 2004
    ....
  88. ncbi Resistance to imatinib (Glivec): update on clinical mechanisms
    Ellen Weisberg
    Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Drug Resist Updat 6:231-8. 2003
    ..Established mechanisms of resistance to imatinib are discussed, as are novel therapeutic approaches to improving drug responsiveness by reversing development of imatinib resistance in patients...
  89. ncbi Patupilone (epothilone B) inhibits growth and survival of multiple myeloma cells in vitro and in vivo
    Boris Lin
    Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Blood 105:350-7. 2005
    ..Taken together, these preclinical findings suggest that patupilone may be a safe and effective drug in the treatment of MM, providing the framework for clinical studies to improve patient outcome in MM...
  90. ncbi After chronic myelogenous leukemia: tyrosine kinase inhibitors in other hematologic malignancies
    Martha Wadleigh
    Division of Hematologic Malignancy, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 105:22-30. 2005
    ..This review focuses on tyrosine kinases that have been implicated in the pathogenesis of hematologic diseases other than chronic myelogenous leukemia and discusses the evidence for the use of small molecules to target these kinases...
  91. ncbi Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412
    Richard M Stone
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 105:54-60. 2005
    ..PKC412 is an oral tyrosine kinase inhibitor with clinical activity in patients with AML whose blasts have an activating mutation of FLT3, suggesting potential use in combination with active agents, such as chemotherapy...
  92. ncbi Modulation of Notch signaling by mastermind-like (MAML) transcriptional co-activators and their involvement in tumorigenesis
    Lizi Wu
    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Semin Cancer Biol 14:348-56. 2004
    ..The mounting biochemical and functional evidence indicate that the MAML genes are critical components of the Notch signaling pathway, likely regulating cellular events involved in both normal development and oncogenesis...
  93. ncbi Stable expression of small interfering RNA sensitizes TEL-PDGFbetaR to inhibition with imatinib or rapamycin
    Jing Chen
    Howard Hughes Medical Institute, Division of Hematology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 113:1784-91. 2004
    ..Although siRNA delivery in vivo is a challenging problem, stable expression of siRNA, which targets oncogenic fusion genes, may potentiate the effects of conventional therapy for hematologic malignancies...
  94. ncbi FLT3 tyrosine kinase as a target in acute leukemias
    James D Griffin
    Dana Farber Cancer Institute, Boston, MA, USA
    Hematol J 5:S188-90. 2004
  95. ncbi Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AML
    Jingrui Jiang
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, D720C, Boston, MA 02115, USA
    Blood 104:1855-8. 2004
    ..These results suggest that mutations at N841 represent a significant new activating mutation in patients with AML and that patients with such mutations may respond to small-molecule FLT3 inhibitors such as PKC412...
  96. ncbi Imatinib (STI571) resistance in chronic myelogenous leukemia: molecular basis of the underlying mechanisms and potential strategies for treatment
    Sandra W Cowan-Jacob
    Novartis Institutes of Biomedical Research, CH 4057, Basel, Switzerland
    Mini Rev Med Chem 4:285-99. 2004
    ..Strategies to potentially circumvent or overcome resistance are discussed...
  97. ncbi Cloning and functional characterization of the murine mastermind-like 1 (Maml1) gene
    Lizi Wu
    Department of Medical Oncology, Mayer 540, Dana Farber Cancer Institute, Brigham and Women s Hospital and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Gene 328:153-65. 2004
    ..There seems to be close correlation of the spatial and temporal expression among Maml1, Notch1 and Hes1 in the central nervous system (CNS) during early development, implicating a role for the Maml1 gene in neurogenesis...
  98. ncbi The TEL/ARG leukemia oncogene promotes viability and hyperresponsiveness to hematopoietic growth factors
    Keiko Okuda
    Department of Health Sciences and Preventive Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
    Int J Hematol 79:138-46. 2004
    ..Nonetheless, the hyperresponsiveness to growth factors reported here is more likely to contribute to the pathogenesis of leukemia...
  99. ncbi FLT3 receptors with internal tandem duplications promote cell viability and proliferation by signaling through Foxo proteins
    Blanca Scheijen
    Department of Medical Oncology, Dana Farber Cancer Institute, Mayer 540, 44 Binney Street, Boston, MA 02115, USA
    Oncogene 23:3338-49. 2004
    ..These data indicate that the oncogenic tyrosine kinase FLT3 can negatively regulate Foxo transcription factors, thereby promoting cell survival and proliferation...
  100. ncbi Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs
    M Golam Mohi
    Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, New Research Building, 330 Brookline Avenue, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 101:3130-5. 2004
    ..Similar strategies may be useful for treating solid tumors associated with mutant and/or overexpressed PTKs...
  101. ncbi NPM-ALK fusion kinase of anaplastic large-cell lymphoma regulates survival and proliferative signaling through modulation of FOXO3a
    Ting Lei Gu
    Division of Hematology, Brigham and Women s Hospital Harvard Medical School, 75 Francis Street, Boston, MA, USA
    Blood 103:4622-9. 2004
    ..Thus, FOXO3a is a barrier to hematopoietic transformation that is overcome by phosphorylation and cytoplasmic relocalization induced by the expression of NPM-ALK...

Research Grants16

  1. Regulation of Hematopoiesis by Notch Receptors
    James Griffin; Fiscal Year: 2006
    ..abstract_text> ..
  2. Regulation of Hematopoiesis by Notch Receptors
    James Griffin; Fiscal Year: 2003
    ..abstract_text> ..
  3. SURFACE ANTIGENS OF HUMAN MYELOID PROGENITOR CELLS
    James Griffin; Fiscal Year: 1993
    ..It is anticipated that an improved knowledge of the mechanisms of regulation of normal stem cells may also be ultimately useful in understanding the abnormal regulation of myelopoiesis in disorders such as AML...
  4. Regulation of Hematopoiesis by Notch Receptors
    James Griffin; Fiscal Year: 2007
    ..abstract_text> ..