Profile

Irwin D. Bernstein, MD

Irwin D. Bernstein, MD

Hematology-Oncology

On staff since July 1973

Children's Title: Chief, Division of Hematology/Oncology/Bone Marrow Transplantation; Director, Research Center for Childhood Cancer

Academic Title: Professor

Research Center: Ben Towne Center for Childhood Cancer Research

Irwin D. Bernstein, MD, is chief of the Division of Hematology/Oncology and Bone Marrow Transplant at Seattle Children's Hospital and professor of pediatrics at the University of Washington School of Medicine. He is director of the Division of Pediatric Hematology/Oncology in the university Department of Pediatrics and head of the Pediatric Oncology Program at Fred Hutchinson Cancer Research Center (FHCRC). Bernstein holds the John R. Hartmann Endowed Chair in Pediatric Oncology/Hematology at Seattle Children's and is an American Cancer Society professor.

He has been a board member for the Leukemia and Lymphoma Society, is chairman of the societys Professional Education Committee and is a member of the Scientific Advisory Board for the University of Minnesota Cancer Center. Bernstein's research interests include normal and leukemic hematopoietic stem cells, antibody targeted therapies for lymphoma and leukemia, and the biology of acute myeloid leukemia. He is principal investigator on a Leukemia and Lymphoma Society SCOR program in immunotherapy of hematologic malignancies, as well as multiple other grants, including a Program Project Grant and a U01 grant as a member of the NHLBI stem cell consortium. Dr. Bernstein's studies which have led to the development of concepts of targeting leukemic stem cells for therapeutic purposes and have led to a novel approach for expanding stem cell numbers in cord blood. This latter approach is being tested in a clinical trial to improve cord blood transplantation. Bernstein also heads NIH-supported grants for career development in pediatric and medical oncology, and for pediatric oncology research training.

Overview

Board Certification(s)

Pediatrics
Pediatric Hematology-Oncology

Medical/Professional School

New York University School of Medicine, New York

Research Focus Area

Cancer

Publications

  • Pollard JA, Alonzo TA, Gerbing RB, Ho PA, Zeng R, Ravindranath Y, Dahl G, Lacayo NJ, Becton D, Chang M, Weinstein HJ, Hirsch B, Raimondi SC, Heerema NA, Woods WG, Lange BJ, Hurwitz C, Arceci RJ, Radich JP, Bernstein ID, Heinrich MC, Meshinchi S
    Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML.
    Blood , 2010 Mar. 25 : 2372-9
  • Butler JM, Nolan DJ, Vertes EL, Varnum-Finney B, Kobayashi H, Hooper AT, Seandel M, Shido K, White IA, Kobayashi M, Witte L, May C, Shawber C, Kimura Y, Kitajewski J, Rosenwaks Z, Bernstein ID, Rafii S
    Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells.
    Cell stem cell , 2010 Mar. 5 : 251-64
  • Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger RL, Bernstein ID
    Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution.
    Nature medicine , 2010 Feb. : 232-6
  • Gutman JA, Turtle CJ, Manley TJ, Heimfeld S, Bernstein ID, Riddell SR, Delaney C
    Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit.
    Blood , 2010 Jan. 28 : 757-65
  • Laurenti E, Varnum-Finney B, Wilson A, Ferrero I, Blanco-Bose WE, Ehninger A, Knoepfler PS, Cheng PF, MacDonald HR, Eisenman RN, Bernstein ID, Trumpp A
    Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.
    Cell stem cell , 2008 Dec. 4 : 611-24
  • Yang Q, Kardava L, St Leger A, Martincic K, Varnum-Finney B, Bernstein ID, Milcarek C, Borghesi L
    E47 controls the developmental integrity and cell cycle quiescence of multipotential hematopoietic progenitors.
    Journal of immunology (Baltimore, Md. : 1950) , 2008 Nov. 1 : 5885-94
  • Minella AC, Loeb KR, Knecht A, Welcker M, Varnum-Finney BJ, Bernstein ID, Roberts JM, Clurman BE
    Cyclin E phosphorylation regulates cell proliferation in hematopoietic and epithelial lineages in vivo.
    Genes & development , 2008 June 15 : 1677-89
  • Dayyani F, Wang J, Yeh JR, Ahn EY, Tobey E, Zhang DE, Bernstein ID, Peterson RT, Sweetser DA
    Loss of TLE1 and TLE4 from the del(9q) commonly deleted region in AML cooperates with AML1-ETO to affect myeloid cell proliferation and survival.
    Blood , 2008 Apr, 15 : 4338-47
  • Varnum-Finney B, Dallas MH, Kato K, Bernstein ID
    Notch target Hes5 ensures appropriate Notch induced T- versus B-cell choices in the thymus.
    Blood , 2008 Mar. 1 : 2615-20
  • Walter RB, Häusermann P, Raden BW, Teckchandani AM, Kamikura DM, Bernstein ID, Cooper JA
    Phosphorylated ITIMs enable ubiquitylation of an inhibitory cell surface receptor.
    Traffic (Copenhagen, Denmark) , 2008 Feb. : 267-79
  • Walter RB, Raden BW, Zeng R, Häusermann P, Bernstein ID, Cooper JA
    ITIM-dependent endocytosis of CD33-related Siglecs: role of intracellular domain, tyrosine phosphorylation, and the tyrosine phosphatases, Shp1 and Shp2.
    Journal of leukocyte biology , 2008 Jan. : 200-11
  • Bernstein ID, Boyd RL, van den Brink MR
    Clinical strategies to enhance posttransplant immune reconstitution.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation , 2008 Jan. : 94-9
  • Aoyama K, Delaney C, Varnum-Finney B, Kohn AD, Moon RT, Bernstein ID
    The interaction of the Wnt and Notch pathways modulates natural killer versus T cell differentiation.
    Stem cells (Dayton, Ohio) , 2007 Oct. : 2488-97
  • Walter RB, Gooley TA, van der Velden VH, Loken MR, van Dongen JJ, Flowers DA, Bernstein ID, Appelbaum FR
    CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy.
    Blood , 2007 May 15 : 4168-70
  • Dallas MH, Varnum-Finney B, Martin PJ, Bernstein ID
    Enhanced T-cell reconstitution by hematopoietic progenitors expanded ex vivo using the Notch ligand Delta1.
    Blood , 2007 Apr, 15 : 3579-87
  • Pollard JA, Alonzo TA, Gerbing RB, Woods WG, Lange BJ, Sweetser DA, Radich JP, Bernstein ID, Meshinchi S
    FLT3 internal tandem duplication in CD34+/CD33- precursors predicts poor outcome in acute myeloid leukemia.
    Blood , 2006 Oct. 15 : 2764-9
  • Pagel JM, Appelbaum FR, Eary JF, Rajendran J, Fisher DR, Gooley T, Ruffner K, Nemecek E, Sickle E, Durack L, Carreras J, Horowitz MM, Press OW, Gopal AK, Martin PJ, Bernstein ID, Matthews DC
    131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission.
    Blood , 2006 Mar. 1 : 2184-91
  • Sweetser DA, Peniket AJ, Haaland C, Blomberg AA, Zhang Y, Zaidi ST, Dayyani F, Zhao Z, Heerema NA, Boultwood J, Dewald GW, Paietta E, Slovak ML, Willman CL, Wainscoat JS, Bernstein ID, Daly SB
    Delineation of the minimal commonly deleted segment and identification of candidate tumor-suppressor genes in del(9q) acute myeloid leukemia.
    Genes, chromosomes & cancer , 2005 Nov. : 279-91
  • Delaney C, Varnum-Finney B, Aoyama K, Brashem-Stein C, Bernstein ID
    Dose-dependent effects of the Notch ligand Delta1 on ex vivo differentiation and in vivo marrow repopulating ability of cord blood cells.
    Blood , 2005 Oct. 15 : 2693-9
  • Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH, Dombret H, Theobald M, Voliotis D, Bennett JM, Richie M, Leopold LH, Berger MS, Sherman ML, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR
    Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence.
    Cancer , 2005 Oct. 1 : 1442-52
  • Dallas MH, Varnum-Finney B, Delaney C, Kato K, Bernstein ID
    Density of the Notch ligand Delta1 determines generation of B and T cell precursors from hematopoietic stem cells.
    The Journal of experimental medicine , 2005 May 2 : 1361-6
  • Walter RB, Raden BW, Kamikura DM, Cooper JA, Bernstein ID
    Influence of CD33 expression levels and ITIM-dependent internalization on gemtuzumab ozogamicin-induced cytotoxicity.
    Blood , 2005 Feb. 1 : 1295-302
  • Hallahan AR, Pritchard JI, Hansen S, Benson M, Stoeck J, Hatton BA, Russell TL, Ellenbogen RG, Bernstein ID, Beachy PA, Olson JM
    The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas.
    Cancer research , 2004 Nov. 1 : 7794-800
  • Walter RB, Raden BW, Cronk MR, Bernstein ID, Appelbaum FR, Banker DE
    The peripheral benzodiazepine receptor ligand PK11195 overcomes different resistance mechanisms to sensitize AML cells to gemtuzumab ozogamicin.
    Blood , 2004 June 1 : 4276-84
  • Delaney C, Bernstein ID
    Establishment of a pluripotent preleukaemic stem cell line by expression of the AML1-ETO fusion protein in Notch1-immortalized HSCN1cl10 cells.
    British journal of haematology , 2004 May : 353-7
  • Johnston DL, Meshinchi S, Opheim KE, Pallavicini MG, Feusner J, Woods WG, Lange BJ, Radich JP, Bernstein ID
    Progenitor cell involvement is predictive of response to induction chemotherapy in paediatric acute myeloid leukaemia.
    British journal of haematology , 2003 Nov. : 431-5
  • Beeson C, Butrynski JE, Hart MJ, Nourigat C, Matthews DC, Press OW, Senter PD, Bernstein ID
    Conditionally cleavable radioimmunoconjugates: a novel approach for the release of radioisotopes from radioimmunoconjugates.
    Bioconjugate chemistry , 2003 Sept. : 927-33
  • Walter RB, Raden BW, Hong TC, Flowers DA, Bernstein ID, Linenberger ML
    Multidrug resistance protein attenuates gemtuzumab ozogamicin-induced cytotoxicity in acute myeloid leukemia cells.
    Blood , 2003 Aug. 15 : 1466-73
  • Meshinchi S, Stirewalt DL, Alonzo TA, Zhang Q, Sweetser DA, Woods WG, Bernstein ID, Arceci RJ, Radich JP
    Activating mutations of RTK/ras signal transduction pathway in pediatric acute myeloid leukemia.
    Blood , 2003 Aug. 15 : 1474-9
  • Sievers EL, Lange BJ, Alonzo TA, Gerbing RB, Bernstein ID, Smith FO, Arceci RJ, Woods WG, Loken MR
    Immunophenotypic evidence of leukemia after induction therapy predicts relapse: results from a prospective Children's Cancer Group study of 252 patients with acute myeloid leukemia.
    Blood , 2003 May 1 : 3398-406
  • Varnum-Finney B, Brashem-Stein C, Bernstein ID
    Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability.
    Blood , 2003 Mar. 1 : 1784-9
  • Ohishi K, Varnum-Finney B, Bernstein ID
    Delta-1 enhances marrow and thymus repopulating ability of human CD34(+)CD38(-) cord blood cells.
    The Journal of clinical investigation , 2002 Oct. : 1165-74
  • Gopal AK, Rajendran JG, Petersdorf SH, Maloney DG, Eary JF, Wood BL, Gooley TA, Bush SA, Durack LD, Martin PJ, Matthews DC, Appelbaum FR, Bernstein ID, Press OW
    High-dose chemo-radioimmunotherapy with autologous stem cell support for relapsed mantle cell lymphoma.
    Blood , 2002 May 1 : 3158-62
  • Bernstein ID
    CD33 as a target for selective ablation of acute myeloid leukemia.
    Clinical lymphoma , 2002 Mar. : S9-11
  • Linenberger ML, Maloney DG, Bernstein ID
    Antibody-directed therapies for hematological malignancies.
    Trends in molecular medicine , 2002 Feb. : 69-76