PHS 398/2590 (Rev. 06/09), Biographical Sketch Format Page s3

Program Director/Principal Investigator (Last, First, Middle): George, Tracy, Irene

BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES.

NAME POSITION TITLE George, Tracy I. Associate Professor of Pathology eRA COMMONS USER NAME (credential, e.g., agency login)

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) DEGREE INSTITUTION AND LOCATION MM/YY FIELD OF STUDY (if applicable) University of California, Berkeley BA 05/90 Molecular Biology University of California, San Francisco MD 06/95 Medicine University of California, San Francisco 06/98 Pathology & Lab Medicine Stanford University 06/99 Surgical Pathology University of California, San Francisco 06/00 Laboratory Medicine Stanford University 06/01 Hematopathology

A. Personal Statement Myeloproliferative neoplasms are the main focus of my research. As background, myeloproliferative neoplasms have become a hot topic in the area of hematology with the description of mutations in genes encoding protein tyrosine kinases (i.e., JAK2, PDGFR, KIT mutations) resulting in constitutively abnormal protein tyrosine kinases leading to activation of signal transduction pathways resulting in abnormal cellular proliferation. These pathways are now targets for therapy using tyrosine kinase inhibitors (TKI). One very rare myeloproliferative neoplasm is mastocytosis, a disease of abnormal mast cells, typically associated with a D816V mutation in the KIT gene. I first became interested in this topic at Stanford University when collaborating with Dr. Jason Gotlib on a “bench to bedside” project showing activity in mast cell leukemia, a highly aggressive and rare disease for which there was no known effective treatment. Using a TKI (PKC412, midostaurin), which has shown activity in a cell line with the D816V KIT mutation, we demonstrated clinical and marrow response in a patient with the same mutation in her mast cell leukemia (ref 1). The results from this study prompted a phase II clinical trial initiated by Dr. Gotlib for the use of midostaurin in patients with aggressive mast cell disease, with myself as the pathologist. In the course of this clinical trial, I diagnosed an extremely rare form of acute leukemia, known as myelomastocytic leukemia, an aggressive disease characterized by immature mast cells and myeloblasts. This type of acute leukemia has not yet been recognized by the World Health Organization and most hematologists and pathologists are unfamiliar with its clinical and pathologic findings. In Arredondo et al., we compared 3 diagnostic challenging cases of acute leukemia highlighting a difficult differential diagnosis that includes myelomastocytic leukemia, mast cell leukemia, and systemic mastocytosis associated with acute myeloid leukemia (ref 3). These 3 acute leukemias appear morphologically similar at first glance, but careful study of the diagnostic material including morphology, immunophenotyping and genetic studies coupled with clinical and laboratory data lead to the correct diagnosis and subsequent treatment. We also described other unusual forms of systemic mastocytosis (ref 7), including rare morphologic mimics of systemic mastocytosis that need different therapy (ref 9). The interim results of our clinical trial prompted Novartis to initiate an international multicenter clinical trial, of which I am the pathologist for North America. Collaborations with researchers in this field have led to work on defining better response criteria for patients with advanced mastocytosis (ref 10) and novel diagnostic markers in mast cells (refs 5, 13). Interestingly, a major proportion of patients with systemic mastocytosis have other concurrent myeloid disorders (ref 7), and we have been investigating the frequency of mastocytosis in different myeloid malignancies and the implication of this diagnosis (ref 15, ongoing research). Answers to the pathogenesis of mastocytosis may come using techniques such as comprehensive whole genome sequencing (described in another type of myeloproliferative neoplasm in ref 11). We plan to pursue investigations into mastocytosis and other myeloproliferative neoplasms using insights into the genetics of these diseases (described in another rare myeloproliferative neoplasm in ref 12).

PHS 398/2590 (Rev. 06/09) Page 1 Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): George, Tracy, Irene B. Positions and Honors Positions and Employment 2001.2002 Pathologist, Central Coast Pathology Consultants, San Luis Obispo, CA 2002.2004 Clinical Instructor of Pathology, Stanford University 2004-2006 Clinical Assistant Professor of Pathology, Stanford University 2006-2012 Assistant Professor of Pathology, Stanford University 2012 Associate Professor of Pathology, Stanford University; Interim Associate Director of Pediatrics, Anatomic Pathology & Clinical Labs, Lucile Packard Children’s Hospital 2013- Associate Professor of Pathology, University of New Mexico Health Sciences Center Hematopathology Division Chief & Hematopathology Fellowship Director, University of New Mexico

Other Experience and Professional Memberships 1996- Member, American Society of Clinical Pathologists 1996- Member, United States and Canadian Academy of Pathology (USCAP) 1996- Member, College of American Pathologists (CAP) 2001- Member, American Society of Hematology 2002- Member, International Society of Laboratory Hematology 2003- Member, Society for Hematopathology 2005 Moderator for Hematopathology Scientific Session, USCAP Annual Meeting 2005-2008 Member and Vice Chair, Hematology & Clinical Microscopy Resource Committee, CAP 2007- Editorial Board, International Journal of Laboratory Hematology 2009- Member, European Bone Marrow Working Group 2009-2012 Chair, Hematology & Clinical Microscopy Resource Committee, CAP 2010- Editorial Board, American Journal of Clinical Pathology 2010-2013 Council on Scientific Affairs, CAP 2011 Moderator for Hematopathology Scientific Session, USCAP Annual Meeting 2011 Council Member, International Council for Standardization in Haematology 2011-2014 Board of Directors, International Society for Laboratory Hematology 2013 Associate Editor, International Journal of Laboratory Hematology 2013 Guest Editor, Surgical Pathology Clinics 2013 Member, Test Development and Advisory Committee on Hematology, The American Board of Pathology

Honors 2006 Stanford University Faculty Fellows Program 2006 AAMC Early Career Women Faculty Professional Development Seminar 2008 Excellence in Teaching, Stanford University, Stanford, CA 2010 Excellence in Teaching, Stanford University, Stanford, CA

C. Selected Peer-reviewed Publications (Selected from 53 peer-reviewed publications) 1. J Gotlib, C Berube, JD Growney, C-C Chen, TI George, C Williams, T Kajiguchi, J Ruan, SL Lilleberg, JA Durocher, JH Lichy, Y Wang, PS Cohen, D Arber, C Heinrich, L Neckers, S J Galli, D G Gilliland, and SE Coutre. Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation. Blood 2005;106(8):2865-2870. 2. DA Pollyea, TI George, C Corless, J Gotlib. When Yellow Jackets Attack: Recurrent and severe anaphylactic reactions to insect bites and stings. American Journal of Hematology 2009 Dec; 84(12):843-6. 3. AR Arredondo, J Gotlib, L Shier, B Medeiros, K Wong, A Cherry, C Corless, DA Arber, P Valent, TI George. Myelomastocytic leukemia versus mast cell leukemia versus systemic mastocytosis associated with acute myeloid leukemia: a diagnostic challenge. American Journal of Hematology 2010;85(8):600-6. 4. P Valent, M Arock, C Akin, WR Sperr, A Reiter, K Sotlar, K Hartmann, TI George, K Brockow, HC Kluin-Nelemans, J Gotlib, DD Metcalfe, HP Horny. The classification of systemic mastocytosis should include mast cell leukemia (MCL) and systemic mastocytosis with a clonal hematologic non-mast cell lineage disease (SM-AHNMD). Blood 2010; 116:850-1. 5. P Valent, S Cerny-Reiterer, H Herrmann, I Mirkina, TI George, K Sotlar, WR Sperr, H-P Horny. Phenotypic heterogeneity, novel diagnostic markers, and target expression profiles in normal and neoplastic human mast cells. Best Pract Res Clin Hem 2010; 23:369-78. 6. G Wernig, MG Kharas, A Mullally, DS Leeman, R Okabe, T George, DO Clary, DG Gilliland. EXEL−8232, a small- molecule JAK2 inhibitor, effectively treats thrombocytosis and extramedullary hematopoiesis in a murine model of myeloproliferative neoplasm induced by MPLW515L Leukemia 2012;26(4):720-7. 7. C Ustun, NM Savage, J Gotlib, K Bhalla, E Manaloor, TI George. Systemic Mastocytosis with Associated Clonal Hematological Non-Mast-Cell Lineage Disease: A Case Review. Am J Hematol 2012;87(2):191-3.

PHS 398/2590 (Rev. 06/09) Page 1 Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): George, Tracy, Irene 8. TI George. Malignant or Benign Leukocytosis. Hematology Am Soc Hematol Educ Program. 2012;2012: 475-84. 9. NM Savage, RC Johnson, J Gotlib, TI George. Myeloid and Lymphoid Neoplasms with FGFR1 Abnormalities: diagnostic and therapeutic challenges. Am J Hematol 2013; 88(5):427-430. 10. J Gotlib, A Pardanani, C Akin, A Reiter, T George, O Hermine, H Kluin-Nelemans, K Hartmann, WR Sperr, K Brockow, LB Schwartz, A Orfao, DJ DeAngelo, M Arock, K Sotlar, HP Horny, DD Metcalfe, L Escribano, S Verstovsek, A Tefferi, and P Valent. International Working Group-Myeloproliferative Neoplasms Research and Treatment & European Competence Network on Mastocytosis Consensus Response Criteria in Advanced Systemic Mastocytosis. Blood 2013 Mar 28;121(13):2393-401. Epub 2013 Jan 16. 11. JD Merker, KM Roskin, D Ng, C Pan, DG Fisk, JJ King, R Hoh, LM Okumoto, P Abidi, R Hewitt, CD Jones, MJ Clark, B Zhang, AM Cherry, TI George, JM Cherry, M Snyder, SD Boyd, JL Zehnder, AZ Fire, JR Gotlib. Comprehensive whole- genome sequencing of an early-stage primary myelofibrosis patient defines low mutational burden and nonrecurrent candidate genes. Haematologica 2013 Jul 19. [Epub ahead of print] 12. J Gotlib, JE Maxson, TI George, JW Tyner. The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment. Blood 2013 July 29. [Epub ahead of print] 13. JM Morgado, O Perbellini, RC Johnson, C Teodósio, A Matito, I Álvarez-Twose, P Bonadonna, A Zamò, M Jara- Acevedo, A Mayado, A Garcia-Montero, M Mollejo, TI George, R Zanotti, A Orfao, L Escribano and L Sánchez-Muñoz. CD30 expression by bone marrow mast cells from different diagnostic variants of systemic mastocytosis. Histopathology (in press). 14. RC Johnson, L Ma, A Cherry, DA Arber, TI George. B-cell expression and B-cell gene rearrangements in AML with t(8;21)(q22;q22). Am J Clin Pathol (in press). 15. RC Johnson, NM Savage, T Chiang, A Cherry, JR Gotlib, DA Arber, TI George. Hidden Mastocytosis in AML with t(8;21). Am J Clin Pathol (in press).

D. Research Support Ongoing Research Support PKC412D2201 Laboratory Services Agreement; 2009-2013, SPO#44250, International Clinical Trial PKC412 for Aggressive Forms of Systemic Mastocytosis, in which Dr. George is the Pathologist for N. American Trial Patients Funder: Novartis, Inc. Role: PI

Completed Research Support CPKC412A2213; Gotlib (PI), 2005-2012, A Single Arm, Phase II, Open-label Study to Determine the Efficacy of Twice Daily Oral Dosing of PKC412 Administered to Patients with Aggressive Systemic Mastocytosis (ASM) and Mast Cell Leukemia (MCL) +/- Associated Hematological Non-Mast Cell Disorders Funder: Novartis, Inc. Role: Co-Investigator

Hypereosinophilic syndrome Gotlib (PI) 2004-2011 Protocol ID#CSTI571AUS151 Novartis The goal of this phase II clinical trial is to evaluate the effectiveness of Gleevec (imatinib mesylate) in patients with hypereosinophilic syndrome. Role: Co-Investigator

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