7 results on '"William J. Lane"'
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2. Recurrent genetic HLA loss in AML relapsed after matched unrelated allogeneic hematopoietic cell transplantation
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Samantha D. Drinan, Jerome Ritz, William J. Lane, Scott Leppanen, Aaron R. Thorner, Vincent T. Ho, Benjamin L. Ebert, Robert J. Soiffer, Elizabeth A. Morgan, Max Jan, Jonathan Stevens, Natasha Kekre, Sarah Nikiforow, Anwesha Nag, Corey Cutler, Matthew D. Ducar, Jordan Wengrod, Joseph H. Antin, Jane Baronas, Edwin P. Alyea, Bruce M. Wollison, John Koreth, Matthew Leventhal, and R. Coleman Lindsley more...
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0301 basic medicine ,Myeloid ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Human leukocyte antigen ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,HLA Antigens ,Recurrence ,Minor histocompatibility antigen ,Humans ,Transplantation, Homologous ,Medicine ,Alleles ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Immunotherapy ,medicine.disease ,Leukemia, Myeloid, Acute ,Leukemia ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Mutation ,Immunology ,business ,Biomarkers ,Gene Deletion - Abstract
Immune evasion is a hallmark of cancer and a central mechanism underlying acquired resistance to immune therapy. In allogeneic hematopoietic cell transplantation (alloHCT), late relapses can arise after prolonged alloreactive T-cell control, but the molecular mechanisms of immune escape remain unclear. To identify mechanisms of immune evasion, we performed a genetic analysis of serial samples from 25 patients with myeloid malignancies who relapsed ≥1 year after alloHCT. Using targeted sequencing and microarray analysis to determine HLA allele-specific copy number, we identified copy-neutral loss of heterozygosity events and focal deletions spanning class 1 HLA genes in 2 of 12 recipients of matched unrelated-donor HCT and in 1 of 4 recipients of mismatched unrelated-donor HCT. Relapsed clones, although highly related to their antecedent pretransplantation malignancies, frequently acquired additional mutations in transcription factors and mitogenic signaling genes. Previously, the study of relapse after haploidentical HCT established the paradigm of immune evasion via loss of mismatched HLA. Here, in the context of matched unrelated-donor HCT, HLA loss provides genetic evidence that allogeneic immune recognition may be mediated by minor histocompatibility antigens and suggests opportunities for novel immunologic approaches for relapse prevention. more...
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- 2019
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3. Development and validation of a universal blood donor genotyping platform: A multinational prospective study
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Augusto Rendon, John M. Jongerius, Nicholas A. Watkins, Kim Brügger, Nicholas Gleadall, Daniel Duarte, Tiffany C. Timmer, Sara Trompeter, Matthew R. Walker, Jennifer G. Sambrook, David J. Roberts, Christopher J. Penkett, Carolin M. Sauer, Nieke van der Bolt, Barbera Veldhuisen, Shane Grimsley, Colin Brown, Adam S. Butterworth, Michael J. Sweeting, Salih Tuna, Emanuele Di Angelantonio, John Ord, Karyn Megy, Jessie S Luken, C. Ellen van der Schoot, Ilenia Simeoni, Gail Miflin, William J. Lane, Nicole Thornton, Ram Varma, William J. Astle, Connie M. Westhoff, Christopher S. Nelson, Katja van den Hurk, Jeremy Gollub, Kathleen Stirrups, Willem H. Ouwehand, Femmeke J. Prinsze, Alexander T. Dilthey, John Danesh, Public and occupational health, Graduate School, AII - Inflammatory diseases, APH - Methodology, and Landsteiner Laboratory more...
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medicine.medical_specialty ,Blood transfusion ,Genotype ,medicine.medical_treatment ,Concordance ,Blood Donors ,Human leukocyte antigen ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Isoantibodies ,medicine ,Humans ,Blood Transfusion ,Prospective Studies ,Typing ,Genotyping ,biology ,Transfusion Medicine ,business.industry ,Transfusion medicine ,Hematology ,Biobank ,Immunology ,biology.protein ,Antibody ,business ,030215 immunology - Abstract
Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non–self-antigens is an unavoidable adverse side effect of transfusion. We describe a universal donor typing platform that could be adopted by blood services worldwide to facilitate a universal extended blood-matching policy and reduce sensitization rates. This DNA-based test is capable of simultaneously typing most clinically relevant red blood cell (RBC), human platelet (HPA), and human leukocyte (HLA) antigens. Validation was performed, using samples from 7927 European, 27 South Asian, 21 East Asian, and 9 African blood donors enrolled in 2 national biobanks. We illustrated the usefulness of the platform by analyzing antibody data from patients sensitized with multiple RBC alloantibodies. Genotyping results demonstrated concordance of 99.91%, 99.97%, and 99.03% with RBC, HPA, and HLA clinically validated typing results in 89 371, 3016, and 9289 comparisons, respectively. Genotyping increased the total number of antigen typing results available from 110 980 to >1 200 000. Dense donor typing allowed identification of 2 to 6 times more compatible donors to serve 3146 patients with multiple RBC alloantibodies, providing at least 1 match for 176 individuals for whom previously no blood could be found among the same donors. This genotyping technology is already being used to type thousands of donors taking part in national genotyping studies. Extraction of dense antigen-typing data from these cohorts provides blood supply organizations with the opportunity to implement a policy of genomics-based precision matching of blood. more...
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- 2020
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4. Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis
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Gail J. Roboz, Sergio Dias, George Lam, William J. Lane, Steven L. Soignet, Raymond P. Warrell, and Shahin Rafii
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Abstract
Arsenic trioxide (As2O3) has recently been used successfully in the treatment of acute promyelocytic leukemia and has been shown to induce partial differentiation and apoptosis of leukemic cells in vitro. However, the mechanism by which As2O3 exerts its antileukemic effect remains uncertain. Emerging data suggest that the endothelium and angiogenesis play a seminal role in the proliferation of liquid tumors, such as leukemia. We have shown that activated endothelial cells release cytokines that may stimulate leukemic cell growth. Leukemic cells, in turn, can release endothelial growth factors, such as vascular endothelial growth factor (VEGF). On the basis of these observations, we hypothesized that As2O3 may interrupt a reciprocal loop between leukemic cells and the endothelium by direct action on both cell types. We have shown that treatment of proliferating layers of human umbilical vein endothelial cells (HUVECs) with a variety of concentrations of As2O3results in a reproducible dose- and time-dependent sequence of events marked by change to an activated morphology, up-regulation of endothelial cell adhesion markers, and apoptosis. Also, treatment with As2O3 caused inhibition of VEGF production in the leukemic cell line HEL. Finally, incubation of HUVECs with As2O3 prevented capillary tubule and branch formation in an in vitro endothelial cell–differentiation assay. In conclusion, we believe that As2O3 interrupts a reciprocal stimulatory loop between leukemic cells and endothelial cells by causing apoptosis of both cell types and by inhibiting leukemic cell VEGF production. more...
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- 2000
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5. Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis
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William J. Lane, Gail J. Roboz, George Lam, Steven L. Soignet, Shahin Rafii, Sergio Dias, and Raymond P. Warrell
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medicine.medical_specialty ,Endothelium ,Cell growth ,Angiogenesis ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Endothelial stem cell ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,chemistry.chemical_compound ,Cytokine ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Internal medicine ,medicine ,Cancer research ,Arsenic trioxide - Abstract
Arsenic trioxide (As2O3) has recently been used successfully in the treatment of acute promyelocytic leukemia and has been shown to induce partial differentiation and apoptosis of leukemic cells in vitro. However, the mechanism by which As2O3 exerts its antileukemic effect remains uncertain. Emerging data suggest that the endothelium and angiogenesis play a seminal role in the proliferation of liquid tumors, such as leukemia. We have shown that activated endothelial cells release cytokines that may stimulate leukemic cell growth. Leukemic cells, in turn, can release endothelial growth factors, such as vascular endothelial growth factor (VEGF). On the basis of these observations, we hypothesized that As2O3 may interrupt a reciprocal loop between leukemic cells and the endothelium by direct action on both cell types. We have shown that treatment of proliferating layers of human umbilical vein endothelial cells (HUVECs) with a variety of concentrations of As2O3results in a reproducible dose- and time-dependent sequence of events marked by change to an activated morphology, up-regulation of endothelial cell adhesion markers, and apoptosis. Also, treatment with As2O3 caused inhibition of VEGF production in the leukemic cell line HEL. Finally, incubation of HUVECs with As2O3 prevented capillary tubule and branch formation in an in vitro endothelial cell–differentiation assay. In conclusion, we believe that As2O3 interrupts a reciprocal stimulatory loop between leukemic cells and endothelial cells by causing apoptosis of both cell types and by inhibiting leukemic cell VEGF production. more...
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- 2000
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6. Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors
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Shahin Rafii, Mathew R. Williams, William J. Lane, Mario Peichev, Malcolm A.S. Moore, Larry Witte, Daniel S. Pereira, Afzal J. Naiyer, Zhenping Zhu, Daniel J. Hicklin, and Mehmet C. Oz
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Pathology ,medicine.medical_specialty ,Plating efficiency ,Endothelium ,Angiogenesis ,Immunology ,CD34 ,Hematopoietic stem cell ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Molecular biology ,Endothelial progenitor cell ,Endothelial stem cell ,Vascular endothelial growth factor A ,medicine.anatomical_structure ,medicine - Abstract
Emerging data suggest that a subset of circulating human CD34+ cells have phenotypic features of endothelial cells. Whether these cells are sloughed mature endothelial cells or functional circulating endothelial precursors (CEPs) is not known. Using monoclonal antibodies (MoAbs) to the extracellular domain of the human vascular endothelial receptor-2 (VEGFR-2), we have shown that 1.2 ± 0.3% of CD34+ cells isolated from fetal liver (FL), 2 ± 0.5% from mobilized peripheral blood, and 1.4 ± 0.5% from cord blood were VEGFR-2+. In addition, most CD34+VEGFR-2+ cells express hematopoietic stem cell marker AC133. Because mature endothelial cells do not express AC133, coexpression of VEGFR-2 and AC133 on CD34+ cells phenotypically identifies a unique population of CEPs. CD34+VEGFR-2+ cells express endothelial-specific markers, including VE-cadherin and E-selectin. Also, virtually all CD34+VEGFR-2+ cells express the chemokine receptor CXCR4 and migrate in response to stromal-derived factor (SDF)-1 or VEGF. To quantitate the plating efficiency of CD34+ cells that give rise to endothelial colonies, CD34+ cells derived from FL were incubated with VEGF and fibroblast growth factor (FGF)-2. Subsequent isolation and plating of nonadherent FL-derived VEGFR-2+ cells with VEGF and FGF-2 resulted in differentiation of AC133+VEGFR-2+ cells into adherent AC133−VEGFR-2+Ac-LDL+(acetylated low-density lipoprotein) colonies (plating efficiency of 3%). In an in vivo human model, we have found that the neo-intima formed on the surface of left ventricular assist devices is colonized with AC133+VEGFR-2+ cells. These data suggest that circulating CD34+ cells expressing VEGFR-2 and AC133 constitute a phenotypically and functionally distinct population of circulating endothelial cells that may play a role in neo-angiogenesis. more...
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- 2000
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7. Next Generation Sequencing for Blood Group Antigen Profiling
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William J. Lane
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Whole genome sequencing ,Immunology ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Genome ,Antigen ,ABO blood group system ,Genotype ,Human genome ,Allele ,Reference genome - Abstract
There are over 300 serologically defined red blood cell (RBC) antigens and 33 serologically defined platelet antigens, most of which have known genetic changes in 45 RBC or 6 platelet genes that correlate with antigen expression. Exposure to non-self RBC antigens during transfusion or pregnancy can lead to the development of alloantibodies, which on re-exposure can lead to clinically significant and even fatal complications. Therefore, it is vital to know which antigens are present on RBCs. However, traditional serologic phenotyping methods are labor intensive, costly, sometimes unreliable, and reagents are not always available. As such, routine antigen typing is only done for ABO and D antigens. A large percentage of blood is given for hematologic malignancies that will soon get routine whole genome sequencing (WGS). For a minor added cost this data could be used for RBC antigen prediction. However, there are no published reports of using WGS data to predict RBC antigens. This is likely for several reasons: (1) none of the existing WGS data sets have paired serologic RBC phenotypes, (2) there are no fully annotated and complete databases of genotypes to phenotypes, (3) all of the known alleles are defined using cDNAs numbered relative to the start codon without human genome coordinates, and (4) lack of software capable of automated RBC antigen prediction. We have created a fully interactive web site of all known blood group genotype to phenotype correlations, fully annotated with relevant information, and mapped to and visually overlaid to their corresponding human reference genome gene sequences, with algorithms to predict antigen phenotypes from inputted sequences. These predictions are part of the General Genome Reports for the 100 patients getting WGS as part of The MedSeq Project. In addition, each patient is undergoing an extensive antigen phenotypic workup using traditional blood bank serology and currently available SNP PCR based assays, which are being used to validate and improve our prediction strategies. As clinical WGS becomes pervasive we hope that comprehensive blood group prediction will be done on everyone, allowing for easy identification of rare donors and the prevention of alloantibody formation using extended upfront matching of antigens from sequenced recipients and donor. Disclosures No relevant conflicts of interest to declare. more...
- Published
- 2016
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