Bio

Clinical Focus


  • Anatomic Pathology
  • Pathology

Academic Appointments


Administrative Appointments


  • Associate Medical Director, Quality for Informatics (2009 - Present)
  • Associate Medical Director, Laboratory Hematology (2007 - Present)

Professional Education


  • Fellowship:Stanford University Medical Center (2005) CA
  • Board Certification: Hematology, American Board of Pathology (2005)
  • Board Certification: Anatomic Pathology, American Board of Pathology (2004)
  • Residency:Stanford University Medical Center (2004) CA
  • Medical Education:UCLA School of Medicine (2001) CA

Research & Scholarship

Current Research and Scholarly Interests


My research interest is in the use of molecular methods to understand and characterize hematopoietic neoplasms. My current work focuses on the use of PCR-based assays for clonal rearrangements in the immunoglobulin heavy chain gene (IGH) and T-cell receptor gene (TCR) for the diagnosis of mature T-cell lymphomas. We recently demonstrated that two of the most common subtypes of PTCL, peripheral T-cell lymphoma, unspecified, and angioimmunoblastic T-cell lymphoma, exhibit clonal rearrangements both TCR and IGH relatively frequently. Our studies suggest that this unexpected result is due to the presence of B-cell proliferations that often complicate these subtypes of PTCL. We hypothesize that immune dysfunction in the locale of PTCL allows for uncontrolled B-cell proliferation, which is a model is similar to that of post-transplant lymphoproliferative disorder. Our current studies are aimed at providing further support for this theory.

We are also evaluating the use of PCR for the TCR gamma chain gene (TCRG) versus the TCR beta chain gene (TCRB) as a target for T-cell clonality for peripheral blood specimens. A canonical TCRG rearrangement that occurs in 1-3% of normal peripheral blood T cells raises the possibility of false positive clonality. Our studies are aimed at determining whether TCRB offers a more specific target for clonality studies.

Teaching

2013-14 Courses


Publications

Journal Articles


  • Evaluation of the Beckman Coulter UniCel DxH 800, Beckman Coulter LH 780, and Abbott Diagnostics Cell-Dyn Sapphire Hematology Analyzers on Adult Specimens in a Tertiary Care Hospital AMERICAN JOURNAL OF CLINICAL PATHOLOGY Tan, B. T., Nava, A. J., George, T. I. 2011; 135 (6): 939-951

    Abstract

    We evaluated the new Beckman Coulter DxH 800 hematology analyzer (Beckman Coulter, Miami, FL) vs the Abbott Diagnostics Cell-Dyn Sapphire (Abbott Diagnostics, Santa Clara, CA) and Beckman Coulter LH 780 hematology analyzers using 430 adult specimens. The DxH 800 provided a CBC and differential that correlated well with those of the Sapphire and LH 780, with most parameters showing correlation coefficients (r) of more than 0.97. In the instrument vs 400-cell manual differential comparison, all 3 instruments showed similar and acceptable accuracy to the reference method except for nucleated RBC (NRBC) enumeration, in which the DxH 800 and Sapphire outperformed the LH 780. We also compared clinical efficiency by determining whether flagged specimens showed abnormalities on a peripheral blood smear as defined by International Council for Standardization in Haematology criteria. The efficiency, sensitivity, and specificity of the DxH 800 were 77.0%, 87.1%, and 73.0%, respectively, compared with the Sapphire at 75.8%, 93.5%, and 68.8%, respectively, and LH 780 at 66.1%, 93.5%, and 55.3%, respectively.

    View details for DOI 10.1309/AJCP1V3UXEIQTSLE

    View details for Web of Science ID 000290826500015

    View details for PubMedID 21571967

  • Evaluation of the Beckman Coulter UniCel DxH 800 and Abbott Diagnostics Cell-Dyn Sapphire Hematology Analyzers on Pediatric and Neonatal Specimens in a Tertiary Care Hospital AMERICAN JOURNAL OF CLINICAL PATHOLOGY Tan, B. T., Nava, A. J., George, T. I. 2011; 135 (6): 929-938

    Abstract

    We evaluated the new UniCel DxH 800 hematology analyzer (Beckman Coulter, Miami, FL) vs the Cell-Dyn Sapphire (Abbott Diagnostics, Santa Clara, CA) using 156 pediatric specimens in Microtainer tubes (Becton Dickinson, Franklin Lakes, NJ). The CBC and differential showed good interinstrument correlation, including WBCs (r = 0.995), RBCs (r = 0.992), hemoglobin (r = 0.998), mean corpuscular volume (r = 0.988), platelets (r = 0.997), neutrophils (r = 0.988), lymphocytes (r = 0.984), monocytes (r = 0.815), eosinophils (r = 0.840), basophils (r = 0.049), and nucleated RBCs (NRBCs; r = 0.906). In the instrument vs 400-cell manual differential comparison, the DxH 800 and Sapphire showed comparable performance for nearly all parameters except for NRBCs, for which the DxH 800 correlated better (r = 0.989) than the Sapphire (r = 0.906). We also compared clinical efficiency by determining whether flagged specimens showed abnormalities on a peripheral blood smear as defined by International Council for Standardization in Haematology criteria. The efficiency of the DxH 800 was 78.0% vs the Sapphire at 68.1%. Both instruments showed identical sensitivity (91.1%), but the specificity for the DxH 800 (71.9%) was higher than that of the Sapphire (57.3%).

    View details for DOI 10.1309/AJCP2EXNSLGGRVSQ

    View details for Web of Science ID 000290826500014

    View details for PubMedID 21571966

  • Anti-CD47 Antibody Synergizes with Rituximab to Promote Phagocytosis and Eradicate Non-Hodgkin Lymphoma CELL Chao, M. P., Alizadeh, A. A., Tang, C., Myklebust, J. H., Varghese, B., Gill, S., Jan, M., Cha, A. C., Chan, C. K., Tan, B. T., Park, C. Y., Zhao, F., Kohrt, H. E., Malumbres, R., Briones, J., Gascoyne, R. D., Lossos, I. S., Levy, R., Weissman, I. L., Majeti, R. 2010; 142 (5): 699-713

    Abstract

    Monoclonal antibodies are standard therapeutics for several cancers including the anti-CD20 antibody rituximab for B cell non-Hodgkin lymphoma (NHL). Rituximab and other antibodies are not curative and must be combined with cytotoxic chemotherapy for clinical benefit. Here we report the eradication of human NHL solely with a monoclonal antibody therapy combining rituximab with a blocking anti-CD47 antibody. We identified increased expression of CD47 on human NHL cells and determined that higher CD47 expression independently predicted adverse clinical outcomes in multiple NHL subtypes. Blocking anti-CD47 antibodies preferentially enabled phagocytosis of NHL cells and synergized with rituximab. Treatment of human NHL-engrafted mice with anti-CD47 antibody reduced lymphoma burden and improved survival, while combination treatment with rituximab led to elimination of lymphoma and cure. These antibodies synergized through a mechanism combining Fc receptor (FcR)-dependent and FcR-independent stimulation of phagocytosis that might be applicable to many other cancers.

    View details for DOI 10.1016/j.cell.2010.07.044

    View details for Web of Science ID 000281523200014

    View details for PubMedID 20813259

  • The Frequency of Immunoglobulin Heavy Chain Gene and T-Cell Receptor gamma-Chain Gene Rearrangements and Epstein-Barr Virus in ALK(+) and ALK(-) Anaplastic Large Cell Lymphoma and Other Peripheral T-Cell Lymphomas JOURNAL OF MOLECULAR DIAGNOSTICS Tan, B. T., Seo, K., Warnke, R. A., Arber, D. A. 2008; 10 (6): 502-512

    Abstract

    We previously identified a relatively high frequency of B-cell proliferations along with simultaneous T-cell receptor gamma-chain gene (TRG) and immunoglobulin heavy chain gene (IGH) rearrangements in a series of angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified. Here, we report on a series of 74 peripheral T-cell lymphoma (PTCL) cases composed entirely of specific PTCL subtypes, including 28 cases of ALK+ anaplastic large-cell lymphoma (ALCL), 35 cases of ALK- ALCL, and 11 cases that represent other specific PTCL subtypes. We performed IGH and TRG gene rearrangement studies and in situ hybridization for Epstein-Barr virus (EBV) to determine the frequency of IGH clonality and to investigate the relationship between EBV, clonality, and associated B-cell proliferations. Using BIOMED-2 PCR assays, we detected TRG clones in 64 of 74 (86%) cases and IGH clones in 6 of 74 (8%) cases, with all IGH-positive cases exhibiting a concurrent TRG clone. Despite the detection of occasional IGH clones, there was no correlation between IGH clonality and EBV, and B-cell proliferations were not identified in any of the cases. These findings suggest that other factors contribute to IGH clonality and demonstrate that, in the absence of an associated B-cell proliferation, IGH clonality occurs infrequently (8%) in specific PTCL subtypes.

    View details for DOI 10.2353/jmoldx.2008.080054

    View details for Web of Science ID 000260533600007

    View details for PubMedID 18832464

  • The Wilms' tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis LEUKEMIA Hosen, N., Shirakata, T., Nishida, S., Yanagihara, M., Tsuboi, A., Kawakami, M., Oji, Y., Oka, Y., Okabe, M., Tan, B., Sugiyama, H., Weissman, I. L. 2007; 21 (8): 1783-1791

    Abstract

    The Wilms' tumor gene WT1 is overexpressed in most of human leukemias regardless of disease subtypes. To characterize the expression pattern of WT1 during normal and neoplastic hematopoiesis, we generated a knock-in reporter green fluorescent protein (GFP) mouse (WT1(GFP/+)) and assayed for WT1 expression in normal and leukemic hematopoietic cells. In normal hematopoietic cells, WT1 was expressed in none of the long-term (LT) hematopoietic stem cells (HSC) and very few (<1%) of the multipotent progenitor cells. In contrast, in murine leukemias induced by acute myeloid leukemia 1 (AML1)/ETO+TEL/PDGFbetaR or BCR/ABL, WT1 was expressed in 40.5 or 38.9% of immature c-kit(+)lin(-)Sca-1(+) (KLS) cells, which contained a subset, but not all, of transplantable leukemic stem cells (LSCs). WT1 expression was minimal in normal fetal liver HSCs and mobilized HSCs, both of which are stimulated for proliferation. In addition, overexpression of WT1 in HSCs did not result in proliferation or expansion of HSCs and their progeny in vivo. Thus, the mechanism by which expansion of WT1-expressing cells occurs in leukemia remains unclear. Nevertheless, our results demonstrate that the WT1(GFP/+) mouse is a powerful tool for analyzing WT1-expressing cells, and they highlight the potential of WT1, as a specific therapeutic target that is expressed in LSCs but not in normal HSCs.

    View details for DOI 10.1038/sj.leu.2404752

    View details for Web of Science ID 000248170100021

    View details for PubMedID 17525726

  • The cancer stem cell hypothesis: a work in progress LABORATORY INVESTIGATION Tan, B. T., Park, C. Y., Ailles, L. E., Weissman, I. L. 2006; 86 (12): 1203-1207

    Abstract

    There is a growing body of evidence that supports the idea that malignant tumors are initiated and maintained by a population of tumor cells that share similar biologic properties to normal adult stem cells. This model, the cancer stem cell (CSC) hypothesis, is based on the observation that tumors, like adult tissues, arise from cells that exhibit the ability to self-renew as well as give rise to differentiated tissue cells. Although the concept of the CSC is not entirely new, advances made over the past two decades in our understanding of normal stem cell biology in conjunction with the recent application of these concepts to experimentally define CSCs have resulted in the identification of CSCs in several human malignancies.

    View details for DOI 10.1038/labinvest.3700488

    View details for Web of Science ID 000242442400001

    View details for PubMedID 17075578

  • The frequency of B- and T-cell gene Rearrangements and Epstein-Barr virus in T-cell lymphomas - A comparison between angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified with and without associated B-cell proliferations JOURNAL OF MOLECULAR DIAGNOSTICS Tan, B. T., Warnke, R. A., Arber, D. A. 2006; 8 (4): 466-475

    Abstract

    We report on a series of 58 cases of angioimmunoblastic T-cell lymphoma (AILT) and 59 cases of peripheral T-cell lymphoma, unspecified (PTCL-NOS). Subsets of cases from both diagnostic groups were complicated by associated B-cell proliferations, and we performed B- and T-cell clonality studies and in situ hybridization for Epstein-Barr virus (EBV) to investigate the relationship between B-cell proliferation, B-cell clonality, and EBV. Using multiplex polymerase chain reaction assays based on the BIOMED-2 collaborative study, we detected TCRgamma T-cell clones in 78 and 81% of AILT and PTCL-NOS cases, respectively, and IGH B-cell clones in 34 and 35% of AILT and PTCL-NOS cases, respectively. The majority of cases contained EBV-positive cells, including 50% of AILT and 57% of PTCL-NOS cases, and cases with B-cell proliferations were more often EBV-positive. Although a relatively high rate of B-cell clonality has been shown for AILT, our findings for PTCL-NOS differ from previous reports in that B-cell clonality was relatively frequent. Overall, a positive B-cell clone correlated, in part, with the presence of a B-cell proliferation but not with EBV. Our findings demonstrate that B-cell clonality is a common finding in AILT and PTCL-NOS, and its presence should not negate the diagnosis established by morphologic, immunophenotypic, and clinical findings.

    View details for DOI 10.2353/jmoldx.2006.060016

    View details for Web of Science ID 000240256600010

    View details for PubMedID 16931587

Stanford Medicine Resources: