Margaret A. Shipp, MD

Margaret A. Shipp, MD

Medical Oncology

Contact Information

Office Phone Number

617-632-3874

Fax

617-632-4734

Appointments

617-632-6140

Biography

Margaret A. Shipp, MD

Dr. Shipp received her MD in 1979 from Washington University School of Medicine, St. Louis, where she also completed an internship and residency in internal medicine at Barnes Hospital. Her research focuses on the biology of normal and malignant B cells and aggressive B-cell lymphomas. Dr. Shipp is the Chief of the Division of Hematologic Neoplasia at DFCI, the Director of the Lymphoma and Myeloma Program of the Dana-Farber/Harvard Cancer Center and a Professor of Medicine at Harvard Medical School.

Researcher

Physician

Douglas S. Miller Chair in Lymphoma
Director, DF/HCC Lymphoma Research Program
Professor of Medicine, Harvard Medical School

Centers/Programs

Stem Cell Transplantation
Lymphoma Program
CNS Lymphoma Center

Clinical Interests

Bone marrow transplantation, Hodgkin disease, Lymphoma

Board Certification

  • Internal Medicine, 1982
  • Medical Oncology, 1985

Fellowship

  • Dana-Farber Cancer Institute, Medical Oncology
  • Washington University School of Medicine, Immunology Research Fellow

Residency

  • Washington University School of Medicine, Internal Medicine

Medical School

  • Washington University School of Medicine

Recent Awards

  • Distinguished Woman in Medicine and Science, Northwestern University School of Medicine 2007
  • Association of American Physicians, 2005
  • Doris Duke Distinquished Clinical Scientist Award 2001
  • Stohlman Scholar, Leukemia Society of America 2000
  • American Society of Clinical Investigation 1996
  • Scholar, Leukemia Society of America 1995

Research

    Research interests

    Our clinical and basic research group focuses on the pathogenesis and treatment of aggressive B-cell lymphomas, particularly the most common lymphoid malignancy, diffuse large B-cell lymphoma (DLBCL) and related variants and Hodgkin lymphoma. We previously led an international effort to identify highly reproducible clinical prognostic factors in patients with aggressive lymphoma (primarily DLBCL) and develop a model to predict patient outcome. Investigators from 16 major centers in the United States, Canada and Europe contributed data on over 3,000 patients to the International Prognostic Factors project and the subsequent development of the International Prognostic Index (IPI). The IPI is now used worldwide to assess the probability that a DLBCL patient will be cured with standard therapy or require more intensive, investigational treatment. In fact, most recent studies of risk-related therapy in DLBCL are based on IPI-defined patient subgroups. The IPI has also been widely applied to other lymphoid neoplasms. Our laboratory is also characterizing molecular bases for the recognized clinical heterogeneity in DLBCL. Earlier studies focused on specific genes and pathways implicated in biology of normal and malignant lymphoid progenitors. For example, our group cloned and characterized one of the first lymphoid differentiation antigens associated with germinal center B-cells and a good risk subtype of DLBCL, CD10. We demonstrated that CD10 was a neutral endopeptidase that regulated peptide-mediated signaling, stromal cell dependent lymphopoiesis and B-cell reconstitution and maturation in vivo. More recently, our group has identified and characterized novel risk-related genes in DLBCL, including the B-cell protein tyrosine phosphatase, PTPROt, which regulates spleen tyrosine kinase (SYK) activity and is itself a BCL6 target, and 2 partner proteins, BAL and BBAP, which play unique roles in DNA damage repair. In addition, we have developed genome-wide approaches to define the unique molecular signatures of specific DLBCL subtypes and more rational therapeutic targets. Our pilot studies identified several signaling pathways associated with resistance to standard therapy. Two of these pathways (PKCbeta and PDE4B/cAMP) have now been credentialed as rational therapeutic targets in DLBCL. Clinical trials of an oral PKCbeta inhibitor in relapsed/refractory DLBCL are completed and studies in newly diagnosed DLBCL are underway. Additional comprehensive analyses of the molecular signatures of large B-cell lymphoma subtypes led to the identification of discrete disease subtypes. In initial studies, we defined the unique molecular signature of MLBCL, an unusual disease primarily affecting young women. These studies uncovered an unanticipated molecular link between MLBCL and classical Hodgkin lymphoma and a shared NF-kappaB survival pathway. Thereafter, we defined three discrete subsets of DLBCLs: Oxidative Phosphorylation; B-cell Receptor/Proliferation (BCR); and Host Response (HR) tumors. HR tumors which were largely defined by their inflammatory/immune cell infiltrate and shared multiple features of histologically defined T-cell histiocyte-rich BCL. BCR-type DLBCLs, which overexpress BCL6 and have more frequent BCL6 translocations, exhibit coordinate regulation of BCL6 target genes and selective sensitivity to BCL6 inhibitors. BCR-type DLBCLs are reliant upon tonic B-cell receptor signaling and uniquely sensitive to targeted inhibition of this critical survival pathway with a spleen tyrosine kinase (SYK) inhibitor. These preclinical observations led to a recently completed national phase I/II clinical trial of an oral SYK inhibitor which exhibited clinical activity in relapsed/refractory DLBCL. Our observations regarding the shared molecular features of MLBCL and classical Hodgkin lymphoma (cHL) prompted additional analyses of the defining features of cHL. In cHL, small numbers of malignant Reed-Sternberg (RS) cells reside within an extensive inflammatory infiltrate. We found that Hodgkin RS cells exhibit AP-1 dependent overexpression of galectin-1 (Gal1), a carbohydrate-binding lectin that selectively inhibits the apoptosis of cytotoxic T cells and Th1 cells, skews the balance toward a Th2 type cytokine profile and favors the expansion/retention of Treg cells. Gal1 represents a novel therapeutic target for restoring immune surveillance in cHL and several additional malignancies. For these reasons, we have now developed neutralizing Gal1 monoclonal antibodies for further clinical evaluation.

    Publications

      • MYD88L265P augments proximal B-cell receptor signaling in large B-cell lymphomas via an interaction with DOCK8. Blood. 2023 Oct 05; 142(14):1219-1232. View in: Pubmed

      • Minimal residual disease in patients with diffuse large B-cell lymphoma undergoing autologous stem cell transplantation. Blood Adv. 2023 09 12; 7(17):4748-4759. View in: Pubmed

      • Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma. Blood. 2023 09 07; 142(10):878-886. View in: Pubmed

      • Diffuse large B-cell lymphomas have spatially defined, tumor immune microenvironments revealed by high-parameter imaging. Blood Adv. 2023 08 22; 7(16):4633-4646. View in: Pubmed

      • Nivolumab for relapsed/refractory classical Hodgkin lymphoma: 5-year survival from pivotal phase 2 CheckMate 205 study. Blood Adv. 2023 Aug 02. View in: Pubmed

      • Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: final analysis of KEYNOTE-170. Blood. 2023 Jul 13; 142(2):141-145. View in: Pubmed

      • MAPS: Pathologist-level cell type annotation from tissue images through machine learning. bioRxiv. 2023 Jun 27. View in: Pubmed

      • DTX3L E3 ligase targets p53 for degradation at poly ADP-ribose polymerase-associated DNA damage sites. iScience. 2023 Apr 21; 26(4):106444. View in: Pubmed

      • The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee. Blood. 2022 09 15; 140(11):1229-1253. View in: Pubmed

      • Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma. Blood. 2021 03 11; 137(10):1353-1364. View in: Pubmed

      • A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma. Nat Med. 2020 09; 26(9):1468-1479. View in: Pubmed

      • PD-1 blockade for diffuse large B-cell lymphoma after autologous stem cell transplantation. Blood Adv. 2020 01 14; 4(1):122-126. View in: Pubmed

      • Pembrolizumab monotherapy in patients with primary refractory classical hodgkin lymphoma who relapsed after salvage autologous stem cell transplantation and/or brentuximab vedotin therapy: KEYNOTE-087 subgroup analysis. Leuk Lymphoma. 2020 04; 61(4):950-954. View in: Pubmed

      • Genomic analyses of PMBL reveal new drivers and mechanisms of sensitivity to PD-1 blockade. Blood. 2019 12 26; 134(26):2369-2382. View in: Pubmed

      • Genomic analyses of flow-sorted Hodgkin Reed-Sternberg cells reveal complementary mechanisms of immune evasion. Blood Adv. 2019 12 10; 3(23):4065-4080. View in: Pubmed

      • The microenvironmental niche in classic Hodgkin lymphoma is enriched for CTLA-4-positive T cells that are PD-1-negative. Blood. 2019 12 05; 134(23):2059-2069. View in: Pubmed

      • Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 12 01; 37(34):3291-3299. View in: Pubmed

      • CXCR4 upregulation is an indicator of sensitivity to B-cell receptor/PI3K blockade and a potential resistance mechanism in B-cell receptor-dependent diffuse large B-cell lymphomas. Haematologica. 2020 05; 105(5):1361-1368. View in: Pubmed

      • Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood. 2019 10 03; 134(14):1144-1153. View in: Pubmed

      • Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. J Clin Oncol. 2019 08 10; 37(23):1997-2007. View in: Pubmed

      • PD-1 blockade with pembrolizumab for classical Hodgkin lymphoma after autologous stem cell transplantation. Blood. 2019 07 04; 134(1):22-29. View in: Pubmed

      • Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study. J Clin Oncol. 2019 02 20; 37(6):481-489. View in: Pubmed

      • Targeted inhibition of PI3Ka/d is synergistic with BCL-2 blockade in genetically defined subtypes of DLBCL. Blood. 2019 01 03; 133(1):70-80. View in: Pubmed

      • Author Correction: Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018 Aug; 24(8):1290-1291. View in: Pubmed

      • Publisher Correction: Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018 Aug; 24(8):1292. View in: Pubmed

      • Mass cytometry of Hodgkin lymphoma reveals a CD4+ regulatory T-cell-rich and exhausted T-effector microenvironment. Blood. 2018 08 23; 132(8):825-836. View in: Pubmed

      • Reply to Z. Wu et al. J Clin Oncol. 2018 09 01; 36(25):2657. View in: Pubmed

      • Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018 05; 24(5):679-690. View in: Pubmed

      • Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018 05 10; 36(14):1428-1439. View in: Pubmed

      • Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma. J Clin Oncol. 2018 04 01; 36(10):942-950. View in: Pubmed

      • Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program. 2017 12 08; 2017(1):310-316. View in: Pubmed

      • Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma. Blood. 2017 11 23; 130(21):2265-2270. View in: Pubmed

      • Topological analysis reveals a PD-L1-associated microenvironmental niche for Reed-Sternberg cells in Hodgkin lymphoma. Blood. 2017 11 30; 130(22):2420-2430. View in: Pubmed

      • Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood. 2017 07 20; 130(3):267-270. View in: Pubmed

      • Combined Anti-VEGF and Anti-CTLA-4 Therapy Elicits Humoral Immunity to Galectin-1 Which Is Associated with Favorable Clinical Outcomes. Cancer Immunol Res. 2017 06; 5(6):446-454. View in: Pubmed

      • Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol. 2017 Jul 01; 35(19):2125-2132. View in: Pubmed

      • PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma. Blood. 2017 06 08; 129(23):3071-3073. View in: Pubmed

      • The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia. J Immunother Cancer. 2016; 4:90. View in: Pubmed

      • Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol. 2016 11 01; 34(31):3733-3739. View in: Pubmed

      • Differential contribution of the mitochondrial translation pathway to the survival of diffuse large B-cell lymphoma subsets. Cell Death Differ. 2017 02; 24(2):251-262. View in: Pubmed

      • Classical Hodgkin Lymphoma with Reduced ß2M/MHC Class I Expression Is Associated with Inferior Outcome Independent of 9p24.1 Status. Cancer Immunol Res. 2016 11; 4(11):910-916. View in: Pubmed

      • Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016 Sep; 17(9):1283-94. View in: Pubmed

      • The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 07 11; 30(1):183. View in: Pubmed

      • Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study. J Clin Oncol. 2016 08 10; 34(23):2698-704. View in: Pubmed

      • Immunomodulatory antibodies for the treatment of lymphoma: Report on the CALYM Workshop. Oncoimmunology. 2016 Jul; 5(7):e1186323. View in: Pubmed

      • NLRC5/MHC class I transactivator is a target for immune evasion in cancer. Proc Natl Acad Sci U S A. 2016 May 24; 113(21):5999-6004. View in: Pubmed

      • PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome. J Clin Oncol. 2016 08 10; 34(23):2690-7. View in: Pubmed

      • The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 04 11; 29(4):574-586. View in: Pubmed

      • Genetic Basis for PD-L1 Expression in Squamous Cell Carcinomas of the Cervix and Vulva. JAMA Oncol. 2016 Apr; 2(4):518-22. View in: Pubmed

      • Diffuse large B-cell lymphoma patient-derived xenograft models capture the molecular and biological heterogeneity of the disease. Blood. 2016 05 05; 127(18):2203-13. View in: Pubmed

      • Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood. 2016 Feb 18; 127(7):869-81. View in: Pubmed

      • The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell. 2015 Apr 09; 161(2):319-32. View in: Pubmed

      • A roadmap for discovery and translation in lymphoma. Blood. 2015 Mar 26; 125(13):2175-7. View in: Pubmed

      • PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015 Jan 22; 372(4):311-9. View in: Pubmed

      • Expression of programmed cell death 1 ligand 2 (PD-L2) is a distinguishing feature of primary mediastinal (thymic) large B-cell lymphoma and associated with PDCD1LG2 copy gain. Am J Surg Pathol. 2014 Dec; 38(12):1715-23. View in: Pubmed

      • Molecular classification of MYC-driven B-cell lymphomas by targeted gene expression profiling of fixed biopsy specimens. J Mol Diagn. 2015 Jan; 17(1):19-30. View in: Pubmed

      • Selective JAK2 inhibition specifically decreases Hodgkin lymphoma and mediastinal large B-cell lymphoma growth in vitro and in vivo. Clin Cancer Res. 2014 May 15; 20(10):2674-83. View in: Pubmed

      • Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors. Cell. 2014 Feb 13; 156(4):744-58. View in: Pubmed

      • Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer Cell. 2013 Dec 09; 24(6):777-90. View in: Pubmed

      • SYK inhibition modulates distinct PI3K/AKT- dependent survival pathways and cholesterol biosynthesis in diffuse large B cell lymphomas. Cancer Cell. 2013 Jun 10; 23(6):826-38. View in: Pubmed

      • PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2013 Jul 01; 19(13):3462-73. View in: Pubmed

      • Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma. Blood. 2013 Apr 25; 121(17):3431-3. View in: Pubmed

      • BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) activation, ubiquitylation, and double-strand DNA repair independent of ATM, MDC1, and RNF8. Mol Cell Biol. 2013 Feb; 33(4):845-57. View in: Pubmed

      • A unique galectin signature in human prostate cancer progression suggests galectin-1 as a key target for treatment of advanced disease. Cancer Res. 2013 Jan 01; 73(1):86-96. View in: Pubmed

      • Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell. 2012 Oct 16; 22(4):547-60. View in: Pubmed

      • Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis and tumorigenesis in Kaposi's sarcoma. J Exp Med. 2012 Oct 22; 209(11):1985-2000. View in: Pubmed

      • Integrative analysis reveals an outcome-associated and targetable pattern of p53 and cell cycle deregulation in diffuse large B cell lymphoma. Cancer Cell. 2012 Sep 11; 22(3):359-72. View in: Pubmed

      • Immunohistochemical detection of MYC-driven diffuse large B-cell lymphomas. PLoS One. 2012; 7(4):e33813. View in: Pubmed

      • Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci U S A. 2012 Mar 06; 109(10):3879-84. View in: Pubmed

      • Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin Cancer Res. 2012 Mar 15; 18(6):1611-8. View in: Pubmed

      • FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature. 2012 Jan 05; 481(7379):90-3. View in: Pubmed

      • Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B-cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas. Am J Surg Pathol. 2011 Oct; 35(10):1531-9. View in: Pubmed

      • Viral induction and targeted inhibition of galectin-1 in EBV+ posttransplant lymphoproliferative disorders. Blood. 2011 Apr 21; 117(16):4315-22. View in: Pubmed

      • Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program. Proc Natl Acad Sci U S A. 2011 Feb 15; 108(7):2873-8. View in: Pubmed

      • The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas. Haematologica. 2010 Dec; 95(12):2056-62. View in: Pubmed

      • Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010 Oct 28; 116(17):3268-77. View in: Pubmed

      • MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1. Clin Cancer Res. 2010 Apr 01; 16(7):2122-30. View in: Pubmed

      • Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2010 Apr 01; 115(13):2578-85. View in: Pubmed

      • BCL6 modulates tonic BCR signaling in diffuse large B-cell lymphomas by repressing the SYK phosphatase, PTPROt. Blood. 2009 Dec 17; 114(26):5315-21. View in: Pubmed

      • BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response. Mol Cell. 2009 Oct 09; 36(1):110-20. View in: Pubmed

      • No evidence for the JAK2 (V617F) or JAK2 exon 12 mutations in primary mediastinal large B-cell lymphoma. Diagn Mol Pathol. 2009 Sep; 18(3):144-9. View in: Pubmed

      • GLEPP1/protein-tyrosine phosphatase phi inhibitors block chemotaxis in vitro and in vivo and improve murine ulcerative colitis. J Biol Chem. 2009 Apr 24; 284(17):11385-95. View in: Pubmed

      • The heat shock protein 90 inhibitor IPI-504 induces apoptosis of AKT-dependent diffuse large B-cell lymphomas. Br J Haematol. 2009 Feb; 144(3):358-66. View in: Pubmed

      • AP1-dependent galectin-1 expression delineates classical hodgkin and anaplastic large cell lymphomas from other lymphoid malignancies with shared molecular features. Clin Cancer Res. 2008 Jun 01; 14(11):3338-44. View in: Pubmed

      • SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood. 2008 Feb 15; 111(4):2230-7. View in: Pubmed

      • The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma. Proc Natl Acad Sci U S A. 2007 Aug 07; 104(32):13134-9. View in: Pubmed

      • BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell. 2007 Aug; 12(2):171-85. View in: Pubmed

      • Integrative analysis reveals 53BP1 copy loss and decreased expression in a subset of human diffuse large B-cell lymphomas. Oncogene. 2008 Jan 10; 27(3):318-22. View in: Pubmed

      • BCL6 programs lymphoma cells for survival and differentiation through distinct biochemical mechanisms. Blood. 2007 Sep 15; 110(6):2067-74. View in: Pubmed

      • High dose CHOP: a phase II study of initial treatment in aggressive non-Hodgkin lymphoma. Cancer and Leukemia Group B 9351. Leuk Lymphoma. 2007 May; 48(5):870-80. View in: Pubmed

      • Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2007 May 01; 25(13):1741-6. View in: Pubmed

      • Transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B cell lymphomas. Proc Natl Acad Sci U S A. 2007 Feb 27; 104(9):3207-12. View in: Pubmed

      • Expression of TRAF1 and nuclear c-Rel distinguishes primary mediastinal large cell lymphoma from other types of diffuse large B-cell lymphoma. Am J Surg Pathol. 2007 Jan; 31(1):106-12. View in: Pubmed

      • Molecular signatures define new rational treatment targets in large B-cell lymphomas. Hematology Am Soc Hematol Educ Program. 2007; 265-9. View in: Pubmed

      • Heterogeneous CD52 expression among hematologic neoplasms: implications for the use of alemtuzumab (CAMPATH-1H). Clin Cancer Res. 2006 Dec 01; 12(23):7174-9. View in: Pubmed

      • Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation. Blood. 2006 Nov 15; 108(10):3428-33. View in: Pubmed

      • BAL1 and BBAP are regulated by a gamma interferon-responsive bidirectional promoter and are overexpressed in diffuse large B-cell lymphomas with a prominent inflammatory infiltrate. Mol Cell Biol. 2006 Jul; 26(14):5348-59. View in: Pubmed

      • FAS death domain deletions and cellular FADD-like interleukin 1beta converting enzyme inhibitory protein (long) overexpression: alternative mechanisms for deregulating the extrinsic apoptotic pathway in diffuse large B-cell lymphoma subtypes. Clin Cancer Res. 2006 Jun 01; 12(11 Pt 1):3265-71. View in: Pubmed

      • Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma. J Exp Med. 2006 Feb 20; 203(2):311-7. View in: Pubmed

      • New concepts in treatment approaches and prognostic factors in aggressive NHL. Clin Adv Hematol Oncol. 2006 Feb; 4(2):107-9. View in: Pubmed

      • Lack of IKBA coding region mutations in primary mediastinal large B-cell lymphoma and the host response subtype of diffuse large B-cell lymphoma. Blood. 2006 Jan 15; 107(2):844-5. View in: Pubmed

      • B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity. J Biol Chem. 2005 Oct 07; 280(40):33756-65. View in: Pubmed

      • NFkappaB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes. Blood. 2005 Aug 15; 106(4):1392-9. View in: Pubmed

      • Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. Clin Cancer Res. 2005 May 01; 11(9):3417-24. View in: Pubmed

      • Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach. Blood. 2005 Aug 15; 106(4):1164-74. View in: Pubmed

      • Case records of the Massachusetts General Hospital. Case 12-2005. A 30-year-old woman with a mediastinal mass. N Engl J Med. 2005 Apr 21; 352(16):1697-704. View in: Pubmed

      • TRAF1 expression and c-Rel activation are useful adjuncts in distinguishing classical Hodgkin lymphoma from a subset of morphologically or immunophenotypically similar lymphomas. Am J Surg Pathol. 2005 Feb; 29(2):196-203. View in: Pubmed

      • Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood. 2005 Mar 01; 105(5):1851-61. View in: Pubmed

      • Tumor cell-mediated induction of the stromal factor stromelysin-3 requires heterotypic cell contact-dependent activation of specific protein kinase C isoforms. J Biol Chem. 2005 Jan 14; 280(2):1272-83. View in: Pubmed

      • The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT-dependent apoptosis in diffuse large B-cell lymphoma. Blood. 2005 Jan 01; 105(1):308-16. View in: Pubmed

      • Modified magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr; 45(4):761-7. View in: Pubmed

      • Active stromelysin-3 (MMP-11) increases MCF-7 survival in three-dimensional Matrigel culture via activation of p42/p44 MAP-kinase. Int J Cancer. 2003 Sep 01; 106(3):355-63. View in: Pubmed

      • The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood. 2003 Dec 01; 102(12):3871-9. View in: Pubmed

      • Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib. Blood. 2003 Dec 01; 102(12):4187-90. View in: Pubmed

      • Demographic and geographic variations of oral health among African Americans based on NHANES III. Community Dent Health. 2003 Jun; 20(2):117-22. View in: Pubmed

      • The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity. J Biol Chem. 2003 Jun 13; 278(24):21930-7. View in: Pubmed

      • Molecular diagnostics. Hematology Am Soc Hematol Educ Program. 2003; 279-93. View in: Pubmed

      • Seventy-two hour continuous infusion flavopiridol in relapsed and refractory mantle cell lymphoma. Leuk Lymphoma. 2002 Apr; 43(4):793-7. View in: Pubmed

      • Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: molecular complete responses are not predictive of progression-free survival. J Clin Oncol. 2002 Mar 01; 20(5):1288-94. View in: Pubmed

      • Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med. 2002 Jan; 8(1):68-74. View in: Pubmed

      • Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells? Am J Surg Pathol. 2001 Oct; 25(10):1277-82. View in: Pubmed

      • 2. Report on the workshop: "Clinical consequences of pathology and prognostic factors in aggressive NHL". Ann Hematol. 2001; 80 Suppl 3:B8-12. View in: Pubmed

      • Stromelysin-3 suppresses tumor cell apoptosis in a murine model. J Cell Biochem. 2001; 82(4):549-55. View in: Pubmed

      • Identification and characterization of two androgen response regions in the human neutral endopeptidase gene. Mol Cell Endocrinol. 2000 Dec 22; 170(1-2):131-42. View in: Pubmed

      • BAL is a novel risk-related gene in diffuse large B-cell lymphomas that enhances cellular migration. Blood. 2000 Dec 15; 96(13):4328-34. View in: Pubmed

      • The angiogenic factor interleukin 8 is induced in non-small cell lung cancer/pulmonary fibroblast cocultures. Cancer Res. 2000 Jan 15; 60(2):269-72. View in: Pubmed

      • PTPROt: an alternatively spliced and developmentally regulated B-lymphoid phosphatase that promotes G0/G1 arrest. Blood. 1999 Oct 01; 94(7):2403-13. View in: Pubmed

      • Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr; 17(4):1244. View in: Pubmed

      • International Consensus Conference on High-Dose Therapy with Hematopoietic Stem Cell Transplantation in Aggressive Non-Hodgkin's Lymphomas: report of the jury. J Clin Oncol. 1999 Jan; 17(1):423-9. View in: Pubmed

      • International Consensus Conference on high-dose therapy with hematopoietic stem-cell transplantation in aggressive non-Hodgkin's lymphomas: report of the jury. Ann Oncol. 1999 Jan; 10(1):13-9. View in: Pubmed

      • The cellular and molecular heterogeneity of the aggressive non-Hodgkin's lymphomas. Curr Opin Oncol. 1998 Sep; 10(5):385-91. View in: Pubmed

      • A directly spliced exon 10-containing CD44 variant promotes the metastasis and homotypic aggregation of aggressive non-Hodgkin's lymphoma. Blood. 1998 Jun 01; 91(11):4282-91. View in: Pubmed

      • Stromelysin-3 is induced in tumor/stroma cocultures and inactivated via a tumor-specific and basic fibroblast growth factor-dependent mechanism. J Biol Chem. 1998 Jan 02; 273(1):618-26. View in: Pubmed

      • The type 2 CD10/neutral endopeptidase 24.11 promoter: functional characterization and tissue-specific regulation by CBF/NF-Y isoforms. Blood. 1997 Jun 01; 89(11):4136-45. View in: Pubmed

      • Early restaging gallium scans predict outcome in poor-prognosis patients with aggressive non-Hodgkin's lymphoma treated with high-dose CHOP chemotherapy. J Clin Oncol. 1997 Apr; 15(4):1631-7. View in: Pubmed

      • Can we improve upon the International Index? Ann Oncol. 1997; 8 Suppl 1:43-7. View in: Pubmed

      • CD10/neutral endopeptidase 24.11 is phosphorylated by casein kinase II and coassociates with other phosphoproteins including the lyn src-related kinase. Blood. 1996 Dec 01; 88(11):4159-65. View in: Pubmed

      • Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine Lewis lung carcinoma. Cancer Res. 1996 Feb 15; 56(4):715-8. View in: Pubmed

      • Phorbol ester-mediated regulation of CD10/neutral endopeptidase transcripts in acute lymphoblastic leukemias. Exp Hematol. 1996 Jan; 24(1):43-8. View in: Pubmed

      • High-dose CHOP as initial therapy for patients with poor-prognosis aggressive non-Hodgkin's lymphoma: a dose-finding pilot study. J Clin Oncol. 1995 Dec; 13(12):2916-23. View in: Pubmed

      • Stromelysin-3 is overexpressed by stromal elements in primary non-small cell lung cancers and regulated by retinoic acid in pulmonary fibroblasts. Cancer Res. 1995 Sep 15; 55(18):4120-6. View in: Pubmed

      • Inflammatory effector mechanisms in asthma. Am J Respir Crit Care Med. 1995 Jul; 152(1):403-7. View in: Pubmed

      • Analysis of the human CD10/neutral endopeptidase 24.11 promoter region: two separate regulatory elements. Blood. 1995 Jun 01; 85(11):3199-207. View in: Pubmed

      • CD10/NEP in non-small cell lung carcinomas. Relationship to cellular proliferation. J Clin Invest. 1994 Nov; 94(5):1784-91. View in: Pubmed

      • Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Ann Oncol. 1994 May; 5(5):397-400. View in: Pubmed

      • Prognostic factors in aggressive non-Hodgkin's lymphoma: who has "high-risk" disease? Blood. 1994 Mar 01; 83(5):1165-73. View in: Pubmed

      • Chemotherapy of non-Hodgkin's aggressive lymphomas. Semin Hematol. 1994 Jan; 31(1):46-69. View in: Pubmed

      • Alternatively spliced CD44 transcripts in diffuse large-cell lymphomas: characterization and comparison with normal activated B cells and epithelial malignancies. Blood. 1993 Dec 15; 82(12):3539-47. View in: Pubmed

      • Hematopoietic differentiation antigens that are membrane-associated enzymes: cutting is the key! Blood. 1993 Aug 15; 82(4):1052-70. View in: Pubmed

      • Inhibition of CD10/neutral endopeptidase 24.11 promotes B-cell reconstitution and maturation in vivo. Proc Natl Acad Sci U S A. 1993 Aug 15; 90(16):7618-22. View in: Pubmed

      • Large-cell and immunoblastic lymphoma of the mediastinum: prognostic features and treatment outcome in 57 patients. J Clin Oncol. 1993 Jul; 11(7):1336-43. View in: Pubmed

      • CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides. J Clin Invest. 1993 May; 91(5):1969-73. View in: Pubmed

      • Opioid receptor agonists and Ca2+ modulation in human B cell lines. J Immunol. 1992 Dec 15; 149(12):4074-81. View in: Pubmed

      • CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation. J Clin Invest. 1992 Dec; 90(6):2517-25. View in: Pubmed

      • CD10/NEP is expressed on Thy-1low B220+ murine B-cell progenitors and functions to regulate stromal cell-dependent lymphopoiesis. Blood. 1992 Oct 15; 80(8):2021-9. View in: Pubmed

      • Prognostic factors in non-Hodgkin's lymphoma. Curr Opin Oncol. 1992 Oct; 4(5):856-62. View in: Pubmed

      • Murine common acute lymphoblastic leukemia antigen (CD10 neutral endopeptidase 24.11). Molecular characterization, chromosomal localization, and modeling of the active site. J Immunol. 1992 May 01; 148(9):2817-25. View in: Pubmed

      • CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung. Proc Natl Acad Sci U S A. 1991 Dec 01; 88(23):10662-6. View in: Pubmed

      • CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide-induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation. Blood. 1991 Oct 01; 78(7):1834-41. View in: Pubmed

      • Drug-related pulmonary toxicity in non-Hodgkin's lymphoma. Comparative results with three different treatment regimens. Cancer. 1991 Aug 15; 68(4):699-705. View in: Pubmed

      • Value of follow-up procedures in patients with large-cell lymphoma who achieve a complete remission. J Clin Oncol. 1991 Jul; 9(7):1196-203. View in: Pubmed

      • Report of the first workshop on prognostic factors in large-cell lymphomas. Ann Oncol. 1991 Feb; 2 Suppl 2:213-7. View in: Pubmed

      • A possible immunoregulatory function for [Met]-enkephalin-Arg6-Phe7 involving human and invertebrate granulocytes. J Neuroimmunol. 1991 Feb; 31(2):97-103. View in: Pubmed

      • Downregulation of enkephalin-mediated inflammatory responses by CD10/neutral endopeptidase 24.11. Nature. 1990 Sep 27; 347(6291):394-6. View in: Pubmed

      • Interaction of immunoactive monokines (interleukin 1 and tumor necrosis factor) in the bivalve mollusc Mytilus edulis. Proc Natl Acad Sci U S A. 1990 Jun; 87(12):4426-9. View in: Pubmed

      • The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen. J Clin Oncol. 1990 Jan; 8(1):84-93. View in: Pubmed

      • Organization of the gene encoding common acute lymphoblastic leukemia antigen (neutral endopeptidase 24.11): multiple miniexons and separate 5' untranslated regions. Proc Natl Acad Sci U S A. 1989 Sep; 86(18):7103-7. View in: Pubmed

      • Patterns of relapse in large-cell lymphoma patients with bulk disease: implications for the use of adjuvant radiation therapy. J Clin Oncol. 1989 May; 7(5):613-8. View in: Pubmed

      • The common acute lymphoblastic leukemia antigen gene maps to chromosomal region 3 (q21-q27). J Immunol. 1989 Jan 01; 142(1):283-7. View in: Pubmed

      • Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 ("enkephalinase"): direct evidence by cDNA transfection analysis. Proc Natl Acad Sci U S A. 1989 Jan; 86(1):297-301. View in: Pubmed

      • Identification of a second transforming gene, rasn, in a human multiple myeloma line with a rearranged c-myc allele. Blood. 1988 Oct; 72(4):1163-7. View in: Pubmed

      • Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein. Proc Natl Acad Sci U S A. 1988 Jul; 85(13):4819-23. View in: Pubmed

      • Four patients with myelodysplastic syndrome with translocation (1;7)(p11;p11) including one patient with independent clones del(7)q22) [corrected] and t(1;7)(q21;q11) Cancer Genet Cytogenet. 1988 Jan; 30(1):83-90. View in: Pubmed

      • Differential expression of nuclear proto-oncogenes in T cells triggered with mitogenic and nonmitogenic T3 and T11 activation signals. J Immunol. 1987 Oct 01; 139(7):2143-8. View in: Pubmed

      • The m-BACOD combination chemotherapy regimen in the treatment of diffuse large cell lymphoma. Semin Hematol. 1987 Apr; 24(2 Suppl 1):2-7. View in: Pubmed

      • Identification of major prognostic subgroups of patients with large-cell lymphoma treated with m-BACOD or M-BACOD. Ann Intern Med. 1986 Jun; 104(6):757-65. View in: Pubmed

      • Effective cisplatin (DDP) based chemotherapy in the treatment of hepatoblastoma. Med Pediatr Oncol. 1985; 13(4):187-90. View in: Pubmed

      • High-dose cytosine arabinoside. Active agent in treatment of non-Hodgkin's lymphoma. Am J Med. 1984 Nov; 77(5):845-50. View in: Pubmed

      • A unique DR-related B cell differentiation antigen. J Immunol. 1983 Nov; 131(5):2458-67. View in: Pubmed

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      Dana-Farber Cancer Institute

      450 Brookline Avenue Mayer 513 Boston, MA 02215
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      Dana-Farber Cancer Institute

      Location Avtar

      Dana-Farber Cancer Institute

      450 Brookline Avenue Mayer 513 Boston, MA 02215
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      42.3374, -71.1082