DOCSLIB.ORG

Adhesion Receptors on Peripheral Blood Leukemic B Cells. a Comparative Study on B Cell Chronic Lymphocytic Leukemia and Related

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Adhesion Receptors on Peripheral Blood Leukemic B Cells. a Comparative Study on B Cell Chronic Lymphocytic Leukemia and Related Leukemia (1997) 11, 408–415 1997 Stockton Press All rights reserved 0887-6924/97 $12.00 Adhesion receptors on peripheral blood leukemic B cells. A comparative study on B cell chronic lymphocytic leukemia and related lymphoma/leukemias G Csanaky1, E Matutes2, JA Vass1, R Morilla2 and D Catovsky2 1Department of Pathology, University Medical School of Pe´cs, Hungary; and 2Academic Department of Haematology and Cytogenetics, The Royal Marsden Hospital, London, UK The expression of a series of adhesion receptors: L-selectins the same disease, or change during the clinical course of the (CD62L): Leu-8, several integrins (LFA-1: CD11a/CD18, VLA-4: disease. For example, in chronic lymphocytic leukemia (CLL), CD49d/CD29 and VLA-5: CD49e/CD29), ICAM-1(CD54) and the the most common of the B lymphoid disorders, clinical staging ‘homing receptor’ (CD44) were investigated by a dual color flow 4,5 cytometry in 56 cases of B cell disorders namely, 39 chronic systems not only consider the degree of anemia and lymphocytic leukemias (CLL), four hairy cell leukemia (HCL), thrombocytopenia, but also splenic and nodal infiltration as seven splenic lymphoma with villous lymphocytes (SLVL) and well as the number of nodal regions involved. Similarly, six other non-Hodgkin’s lymphoma (NHL). The functional dissemination of B-NHL may correlate with bulky disease activity of L-selectins was assessed with L-selectin ligand ana- and resistance to standard therapy. logs (polyphosphomonester core polysaccharide: PPME and fucoidin). Leukemic B cells were identified with phycoerythrin- Since these patterns have proven to be of clinical relevance, conjugated monoclonal antibodies (McAbs) anti-CD19, anti- it seems important to investigate the factors which may play kappa/lambda investigated simultaneously for the expression a role in the dissemination and tissue distribution in these of adhesion receptors estimated with fluorescein-isothiocyan- malignancies. In this context, analysis of interactions between ate (FITC) conjugated McAbs. The percentage of leukemic cells certain receptor and ligand molecules,6,7 which result in the expressing L-selectins (Leu-8) was high in CLL (52% of positive binding of lymphocytes to the endothelial cells and give them cases) and integrin expression (LFA-1, VLA-4, 5) was low (19 and 33%, respectively), while a reverse pattern, low Leu-8 the opportunity to leave the blood via the high endothelial (17%), and a high VLA-4 (77%), was observed in non-CLL cases. venules (HEVs) and enter into the secondary lymphoid organs, The expression of LFA-1 a-chain was variable in non-CLL may give some clues in the patterns of dissemination. Thus, cases, and the LFA-1 heterodimer was expressed on most the attachment of leukemic cells to the endothelium rep- clonal B cell in NHLs (92%). LFA-1 a-chain was detected on resents a crucial step in the spreading of such malignancies. b cells from only one HCL case, while 2 integrin was regularly Over the last few years, there have been a number of reports expressed on hairy cells. VLA-5 integrin was found on a rela- tively small number (26%) of mature B cell leukemias. A remark- on the expression and function of cell-adhesion molecules on able finding was the detection of ICAM-1 in all CLL cases albeit leukemic B cells, however, only few studies have focused on the number of positive cells was significantly lower (P , 0.05) the correlation between the expression of these molecules and compared to non-CLL cases. CD44 was expressed on a high the clinical and laboratory findings.8–16 number of neoplastic cells in all the investigated categories. In this study, we have analyzed circulating neoplastic cells There was no correlation between the expression of the from a variety of B cell diseases, namely CLL and hairy cell adhesion molecules and clinical and laboratory parameters except for CD18 which was expressed on a significantly leukemia (HCL) and B-NHL in leukemic phase for the (P , 0.05) higher number of leukemic cells in CLL with more expression of a number of adhesion molecules which advanced stages. This study demonstrates that even closely included: (1) L-selectins (CD62L) (their functional activity was related B cell leukemia/lymphomas have a certain well defined assessed by biotinylated ligand analogs); (2) some key dimeric and strictly variable adhesion profile which is characteristic of integrins such as LFA-1 (leucocyte function associated the disease entity and therefore, the adhesion profile may offer antigen-1: CD11a/CD18), VLA-4,5 (very late activated: additional information useful for differential diagnosis and study of disease pathogenesis. CD49d/CD29, CD49e/CD29); (3) the intercellular adhesion Keywords: B cell lymphoproliferative disorders; immunopheno- molecule-1 (ICAM-1: CD54) which belongs to the immuno- type; adhesion receptors globulin superfamily, as well as (4) the hyaluron binding pro- tein (homing receptor: CD44). Findings have been correlated to the various disease categories and clinical and laboratory Introduction features such as nodal status, pattern of bone marrow infil- tration, lymphocyte count and progressive vs stable disease. B cell lymphoproliferative disorders encompass a variety of disease entities which can be distinguished on clinical and laboratory features.1,2 Peripheral blood involvement is, as a Materials and methods rule, present in cases of primary leukemias and may be present in B cell non-Hodgkin’s lymphoma (B-NHL), parti- Patients and cell samples cularly in some subtypes such as splenic lymphoma of villous lymphocytes (SLVL) which almost always constantly evolve Peripheral blood cells from 56 patients with a B lymphopro- with leukemia.3 liferative disorder which included: 39 CLL; eight of which had In addition, the dissemination pattern may also differ within more than 10% circulating prolymphocytes (CLL/PL); four HCL, three typical and one HCL-variant and 13 cases of B cell NHL in leukemic phase (.5 × 109/l lymphoma cells) were analyzed. The diagnosis was based on clinical, morphological Correspondence: G Csanaky, Department of Pathology, Marku- sovszky Teaching Hospital, Szombathely, Markusovszky u.3, Hun- and immunological features according to the French–Amer- gary, H-9700 ican–British (FAB) Cooperative Group proposals.1 Received 18 October 1996; accepted 27 November 1996 The clinical data were obtained from the patient files of the Adhesion receptors in mature B cell leukemia/lymphomas G Csanaky et al 409 Royal Marsden Hospital, and a questionnaire was sent to Preparation of biotinylated L-selectin ligand analogs physicians of outside hospitals to collect the relevant clinical (b-PPME and b-fucoidin) data. CLL patients were staged according to Binet and Rai.4,5 The 39 CLL patients included 18 males and 21 females (M/F Amino-derivatives of L-selectin ligand17 analogs, polyphos- ratio: 18/21) with a median age of 64 years (range: 41–91); phomonester (PMME)18,19 and fucoidin20 were first produced the four HCLs were all males with a median age: 50 years as described elsewhere,21 then these derivatives were biotinyl- (range: 42–56); and the B-NHL included seven SLVL (M/F: 4/3, ated with the use of biotinyl-N-hydroxysuccinimide ester median age: 66 years, range: 40–74) and six patients with (BNHS) similarly to some biologically active proteins, such as 22 B-NHL which included four mantle zone, one follicular and antibodies, lectins or polypeptide hormones. one lymphoplasmocytic lymphoma (M/F: 1, median age: 63 Briefly, commercial fucoidin (Sigma, St Louis, MO, USA) years, range: 53–81). was treated with a protease, then dialyzed against running and Nodal involvement (number and site of the involved lymph distilled water. The final product of the dialysis was run to node areas) was graded as follows: G1: no lymph node Sepharose 4B gel filtration, and a high molecular-weight enlargement; G2: one node, or one group of lymph nodes in carbohydrate peak was collected. a localized area; G3: involvement of two or more sites con- The PPME preparation started by a mild acid hydrolysis of H. holstii phosphomannan, then saturated by barium hydrox- tiguous along pathways of lymphatic drainage and limited to ide, and the barium salt of high molecular weight PPME was one side of diaphragm (eg neck and axillae); G4: two or more precipitated by ethanol. After the removal of barium by a cat- noncontiguous sites of involvement on both sides of dia- ion exchange resin, a sodium salt was obtained. The acid phragm; and G5: generalized dissemination (bone marrow, hydrolysis resulted in a pentasaccharide phosphonoester spleen and liver involvement were not considered). (PENT) which was also isolated from the supernatant of bar- The histological patterns of bone marrow infiltration were ium precipitation. Prior reduction with sodium borohydride recorded as nodular, interstitial, mixed (nodular and and mild periodate oxidation, PPME and fucoidin were interstitial) and diffuse. The degree of lymphocytosis was derivatized with hexanediamine. × 9 regarded as high when there were over 50 10 /l circulating The b-PPME and b-fucoidin were produced as follows: lymphocytes; lymphocyte doubling time (LDT) less than 12 20 mg of the amino-derivatives of PPME/fucoidin were dis- months was considered a bad prognostic indicator; anemia solved in 550 ml phosphate-buffered saline (PBS), and 10 mg , , × 9 (Hb 11 g/dl) and thrombocytopenia (platelets 100 10 /l) of BNHS in 200 ml dimethyl-sulfoxide (DMSO). Both solutions were also recorded. The progressive or non-progressive nature were mixed at room temperature, and the mixture was incu- of the disease was determined, considering if the patient bated overnight, then precipitated with three volumes of 95% required treatment for active disease. ethanol, and incubated again for 20 min at −20°C, decanted Peripheral blood mononuclear cells (PBMCs) were isolated and the precipitate was repeatedly washed with ethanol, cen- by Ficoll–Hypaque gradient centrifugation from samples trifuged and dried.
Load more

Recommended publications
  • ORIGINAL ARTICLE Flow Cytometric Protein Expression Profiling As a Systematic Approach for Developing Disease-Specific Assays
    Leukemia (2006) 20, 2102–2110 & 2006 Nature Publishing Group All rights reserved 0887-6924/06 $30.00 www.nature.com/leu ORIGINAL ARTICLE Flow cytometric protein expression profiling as a systematic approach for developing disease-specific assays: identification of a chronic lymphocytic leukaemia-specific assay for use in rituximab-containing regimens AC Rawstron, R de Tute, AS Jack and P Hillmen Haematological Malignancy Diagnostic Service (HMDS), Leeds Teaching Hospitals, Leeds, UK Depletion of disease below the levels detected by sensitive sustained remissions only occur in patients achieving an MRD- minimal residual disease (MRD) assays is associated with negative complete response.12 Therefore MRD is increasingly prolonged survival in chronic lymphocytic leukaemia (CLL). being used as an end point for therapeutic trials, and several Flow cytometric MRD assays are now sufficiently sensitive and rapid to guide the duration of therapy in CLL, but generally rely studies are now using the assessment of MRD to define the on assessment of CD20 expression, which cannot be accurately duration of therapy. measured during and after therapeutic approaches containing Approaches using allele-specific oligonucleotide polymerase rituximab. The aim of this study was to use analytical software chain reaction (ASO-PCR) to the immunoglobulin gene of the developed for microarray analysis to provide a systematic B-CLL cell are generally accepted to show the highest sensitivity approach for MRD flow assay development. Samples from CLL for MRD detection. However, more recent four-colour ap- patients (n ¼ 49), normal controls (n ¼ 21) and other B-lympho- proaches show sensitivities nearing that of ASO-PCR6,11,13 with proliferative disorders (n ¼ 12) were assessed with a panel of 66 antibodies.
    [Show full text]
  • ROR1/CD19 Receptor Complex Promotes Growth of Mantle Cell Lymphoma Cells Independently of the B Cell Receptor–BTK Signaling Pathway † Qian Zhang,* Hong Y
    Published September 18, 2019, doi:10.4049/jimmunol.1801327 Cutting Edge: ROR1/CD19 Receptor Complex Promotes Growth of Mantle Cell Lymphoma Cells Independently of the B Cell Receptor–BTK Signaling Pathway † Qian Zhang,* Hong Y. Wang,* Xiaobin Liu,* Selene Nunez-Cruz,* Mowafaqx Jillab, Olga Melnikov,† Kavindra Nath,‡ Jerry Glickson,‡ and Mariusz A. Wasik*,†, Inhibitors of Bruton tyrosine kinase (BTK), a kinase these mechanisms is of uttermost importance in design- downstream of BCR, display remarkable activity in a ing an appropriate therapeutic strategy to counteract the subset of mantle cell lymphoma (MCL) patients, but reprogramming. the drug resistance remains a considerable challenge. In ROR1 belongs to the receptor tyrosine kinase-like orphan this study, we demonstrate that aberrant expression of receptor (ROR) family and displays very restricted expression ROR1 (receptor tyrosine kinase-like orphan receptor 1), in normal tissues (11, 12). ROR1 is aberrantly expressed in seen in a large subset of MCL, results in BCR/BTK– various malignancies, including small lymphocytic lymphoma/ independent signaling and growth of MCL cells. ROR1 chronic lymphocytic leukemia (SLL/CLL) and MCL. ROR1 forms a functional complex with CD19 to persistently activates signaling molecules, such as RAC-1 and contractin activate the key cell signaling pathways PI3K–AKT and (13, 14), to promote cell proliferation, survival, and migration MEK–ERK in the BCR/BTK–independent manner. (13–15). CD19 is a B cell–specific receptor capable of stimu- lating the growth of malignant B cells (16). In normal This study demonstrates that ROR1/CD19 complex B lymphocytes, it is activated by SRC family kinases and effectively substitutes for BCR–BTK signaling to SYK, both downstream of BCR (17).
    [Show full text]
  • Hematopoietic and Lymphoid Neoplasm Coding Manual
    Hematopoietic and Lymphoid Neoplasm Coding Manual Effective with Cases Diagnosed 1/1/2010 and Forward Published August 2021 Editors: Jennifer Ruhl, MSHCA, RHIT, CCS, CTR, NCI SEER Margaret (Peggy) Adamo, BS, AAS, RHIT, CTR, NCI SEER Lois Dickie, CTR, NCI SEER Serban Negoita, MD, PhD, CTR, NCI SEER Suggested citation: Ruhl J, Adamo M, Dickie L., Negoita, S. (August 2021). Hematopoietic and Lymphoid Neoplasm Coding Manual. National Cancer Institute, Bethesda, MD, 2021. Hematopoietic and Lymphoid Neoplasm Coding Manual 1 In Appreciation NCI SEER gratefully acknowledges the dedicated work of Drs, Charles Platz and Graca Dores since the inception of the Hematopoietic project. They continue to provide support. We deeply appreciate their willingness to serve as advisors for the rules within this manual. The quality of this Hematopoietic project is directly related to their commitment. NCI SEER would also like to acknowledge the following individuals who provided input on the manual and/or the database. Their contributions are greatly appreciated. • Carolyn Callaghan, CTR (SEER Seattle Registry) • Tiffany Janes, CTR (SEER Seattle Registry) We would also like to give a special thanks to the following individuals at Information Management Services, Inc. (IMS) who provide us with document support and web development. • Suzanne Adams, BS, CTR • Ginger Carter, BA • Sean Brennan, BS • Paul Stephenson, BS • Jacob Tomlinson, BS Hematopoietic and Lymphoid Neoplasm Coding Manual 2 Dedication The Hematopoietic and Lymphoid Neoplasm Coding Manual (Heme manual) and the companion Hematopoietic and Lymphoid Neoplasm Database (Heme DB) are dedicated to the hard-working cancer registrars across the world who meticulously identify, abstract, and code cancer data.
    [Show full text]
  • Waldenstro¨M's Macroglobulinemia Is a Biological Syndrome Which May
    Correspondence 1637 cation,10 particularly in acute promyelocytic leukemia (APL), we References searched for genomic similarities. The few specific studies in existence on sequence analysis of the PML-RAR␣ gene show that the breakpoint within the involved gene (usually the PML locus) is variably situated, 1 Saglio G, Guerrasio A, Tassinari A, Ponzetto C, Zaccaria A, Testoni and that the corresponding fusion transcript should be aberrant. The P, Celso B, Rege Cambrin G, Serra A, Pegoraro L. Variability of the ␣ resulting PML-RAR proteins contained residues not homologous with molecular defects corresponding to the presence of a Philadelphia ␣ either PML or RAR . These reported atypical breaks were very similar chromosome in human hematologic malignancies. Blood 1988; to the one recorded in our case. A second original characteristic of 72: 1203–1208. the BCR break reported by us is that an intronic sequence derived 2 Chissoe SL, Bodenteich A, Wang YF, Wang YP, Burian D, Clifton from abl intron Ib was juxtaposed to bcr exon. This is another unpre- SW, Crabtree J, Freeman A, Iyer K, Jian L. Sequence and analysis cedented feature for a CML patient, although on rare occasions it has 10 of the human ABL gene, the BCR gene, and regions involved in been reported in AML patients. So, it may be speculated that in a the Philadelphia chromosomal translocation. Genomics 1995; 27: small proportion of the DNA breaks that occurs in leukemia, a cur- 67–82. rently unknown molecular mechanism could break the coding DNA. 3 Saglio G, Guerrasio A, Rosso C, Zaccaria A, Tassinari A, Serra A, The resulting RNA remains in-frame coding an aberrant or, as in our Rege-Cambrin G, Mazza U, Gavosto F.
    [Show full text]
  • Lymphoproliferative Disorders
    Lymphoproliferative disorders Dr. Mansour Aljabry Definition Lymphoproliferative disorders Several clinical conditions in which lymphocytes are produced in excessive quantities ( Lymphocytosis) Lymphoma Malignant lymphoid mass involving the lymphoid tissues (± other tissues e.g : skin ,GIT ,CNS …) Lymphoid leukemia Malignant proliferation of lymphoid cells in Bone marrow and peripheral blood (± other tissues e.g : lymph nods ,spleen , skin ,GIT ,CNS …) Lymphoproliferative disorders Autoimmune Infection Malignant Lymphocytosis 1- Viral infection : •Infectious mononucleosis ,cytomegalovirus ,rubella, hepatitis, adenoviruses, varicella…. 2- Some bacterial infection: (Pertussis ,brucellosis …) 3-Immune : SLE , Allergic drug reactions 4- Other conditions:, splenectomy, dermatitis ,hyperthyroidism metastatic carcinoma….) 5- Chronic lymphocytic leukemia (CLL) 6-Other lymphomas: Mantle cell lymphoma ,Hodgkin lymphoma… Infectious mononucleosis An acute, infectious disease, caused by Epstein-Barr virus and characterized by • fever • swollen lymph nodes (painful) • Sore throat, • atypical lymphocyte • Affect young people ( usually) Malignant Lymphoproliferative Disorders ALL CLL Lymphomas MM naïve B-lymphocytes Plasma Lymphoid cells progenitor T-lymphocytes AML Myeloproliferative disorders Hematopoietic Myeloid Neutrophils stem cell progenitor Eosinophils Basophils Monocytes Platelets Red cells Malignant Lymphoproliferative disorders Immature Mature ALL Lymphoma Lymphoid leukemia CLL Hairy cell leukemia Non Hodgkin lymphoma Hodgkin lymphoma T- prolymphocytic
    [Show full text]
  • Molecular Design, Optimization and Genomic Integration of Chimeric B
    bioRxiv preprint doi: https://doi.org/10.1101/516369; this version posted June 5, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 1 Molecular design, optimization and genomic integration of chimeric B cell 2 receptors in murine B cells 3 4 Theresa Pesch1, Lucia Bonati1, William Kelton1, Cristina Parola1,2, Roy A Ehling1, Lucia 5 Csepregi1, Daisuke Kitamura3, Sai T ReDDy1,* 6 7 1 Department of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland 8 2 Life Science Graduate School, Systems Biology, ETH Zürich, University of Zurich, Zurich 8057, 9 Switzerland 10 3 Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan 11 *To whom corresponDence shoulD be aDDresseD. Tel: +41 61 387 33 68; Email: [email protected] 12 Key worDs: B cells, synthetic antigen receptor, cellular engineering, genome eDiting, cellular 13 immunotherapy, CRISPR-Cas9 14 15 Abstract 16 Immune cell therapies baseD on the integration of synthetic antigen receptors proviDe 17 a powerful strategy for the treatment of Diverse Diseases, most notably retargeting 18 T cells engineereD to express chimeric antigen receptors (CAR) for cancer therapy. In 19 aDDition to T lymphocytes, B lymphocytes may also represent valuable immune cells 20 that can be engineereD for therapeutic purposes such as protein replacement therapy 21 or recombinant antiboDy proDuction. In this article, we report a promising concept for 22 the molecular Design, optimization anD genomic integration of a novel class of 23 synthetic antigen receptors, chimeric B cell receptors (CBCR).
    [Show full text]
  • | Lymphoproliferative Disorders
    | Lymphoproliferative Hematology 438 teamwork disorders Color index: Red: Important Gray: notes Blue: extra Editing file Not malignant | definitions Lymphoproliferative disorders characters: -mature lymphocytes (no blasts), -lymphocytosis, Lymphoma -chronic. Lymphoid leukemia Several clinical conditions in Malignant proliferation of Malignant lymphoid mass which lymphocytes are lymphoid cells in Bone involving the lymphoid tissues produced in excessive marrow and peripheral blood (± other tissues ie; Extranodal quantities (Lymphocytosis) when the malignancy of lymphocytes reaches the lymphoma, by definition, involves sites other N.B: Lymphoproliferative disorders occur when the normal bone marrow or the peripheral blood we call it than lymph nodes, spleen, thymus and the mechanisms of control of proliferation of lymphocytes break lymphoid leukemia. pharyngeal lymphatic ring. e.g : skin down, resulting in autonomous, uncontrolled proliferation of lymphoid cells and typically leading to lymphocytosis and/or (± other tissues e.g : lymph ,GIT ,CNS) lymphadenopathy, and sometimes to involvement of extranodal sites, e.g. bone marrow. nodes ,spleen , skin ,GIT ,CNS) Autoimmune Infection Malignant Mostly virus Causes of lymphoproliferative disorder: These include (1) malignant—clonal in nature, resulting from the uncontrolled proliferation of a single transformed cell, e.g. lymphoma; (2) nonmalignant—polyclonal lymphoproliferative disorders may result from conditions including (a) infections—lymphocytosis is commonly caused by viral infections, e.g. Epsitein–Barr virus (EBV); lymphadenopathy is a common feature of a very wide variety of infections, (b) reactive—conditions such as systemic lupus erythematosus (SLE) and sarcoidosis frequently cause lymphadenopathy. | Lymphocytosis Blood film is very important, also Age is very important to expect the cause of lymphocytosis. Small lymphocytes: in non-infectious causes ●bacterial infection Some bacteria as ●Chronic lymphocytic ●Viral infection Pertussis ,brucellosis.
    [Show full text]
  • Cd79b Expression in B Cell Chronic Lymphocytic Leukemia: Its Implication for Minimal Residual Disease Detection
    Leukemia (1999) 13, 1501–1505 1999 Stockton Press All rights reserved 0887-6924/99 $15.00 http://www.stockton-press.co.uk/leu CD79b expression in B cell chronic lymphocytic leukemia: its implication for minimal residual disease detection JA Garcia Vela, I Delgado, L Benito, MC Monteserin, L Garcia Alonso, N Somolinos, MA Andreu and F On˜a Department of Hematology, Hospital Universitario de Getafe, Madrid, Spain The surface expression of CD79b, using the monoclonal anti- antigen expression and antigen overexpression) in order to body (Mab) CB3–1, on B lymphocytes from normal individuals establish the applicability of immunophenotypic aberrances and patients with B cell chronic lymphocytic leukemia (CLL) for monitoring MRD as in acute leukemias with a sensitivity has been analyzed using triple-staining cells for flow cytome- −4 try. In addition, the clinical significance of CD79b expression level of 10 (one aberrant CLL cell among 10000 normal in CLL patients and its possible value for the evaluation of mini- cells). We have previously published that CD5 is overex- mal residual disease (MRD) was explored. A total of 15 periph- pressed in most CLL cases.2 This aberrantly CD5high/CD19+ eral blood (PB) samples from healthy blood donors, five bone expression was present in 90% of our CLL. Dilutional experi- marrow (BM) samples from normal donors and 40 PB samples ments showed that CD5high/CD19+ were identified at fre- from CLL untreated patients were included in the study. In −4 addition we studied the expression of CD79b in B lymphocytes quencies as low as 10 . from five CLL patients after fludarabine treatment in order to Recently, different groups have communicated that CD79b support our method.
    [Show full text]
  • Downloaded and Further Processed with the R Programming Language ( and Bioconductor ( Software
    bioRxiv preprint doi: https://doi.org/10.1101/801530; this version posted October 13, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. An integrated multi-omic single cell atlas to redefine human B cell memory David R. Glass,1,2,5 Albert G. Tsai,2,5 John Paul Oliveria,2,3 Felix J. Hartmann,2 Samuel C. Kimmey,2,4 Ariel A. Calderon,1,2 Luciene Borges,2 Sean C. Bendall1,2,6,* 1Immunology Graduate Program, Stanford University, Stanford, CA, 94305, USA 2Department of Pathology, Stanford University, Stanford, CA, 94305, USA 3Department of Medicine, Division of Respirology, McMaster University, Hamilton, ON, L8S4K1, Canada 4Department of Developmental Biology, Stanford, University, Stanford CA, 94305, USA 5Co-first author 6Lead Author *Correspondence: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/801530; this version posted October 13, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Abstract: To evaluate the impact of heterogeneous B cells in health and disease, comprehensive profiling is needed at a single cell resolution. We developed a highly- multiplexed screen to quantify the co-expression of 351 surface molecules on low numbers of primary cells. We identified dozens of differentially expressed molecules and aligned their variance with B cell isotype usage, metabolism, biosynthesis activity, and signaling response.
    [Show full text]
  • Immunotherapies Shape the Treatment Landscape for Hematologic Malignancies Jane De Lartigue, Phd
    Feature Immunotherapies shape the treatment landscape for hematologic malignancies Jane de Lartigue, PhD he treatment landscape for hematologic of TIL therapy has been predominantly limited to malignancies is evolving faster than ever melanoma.1,3,4 before, with a range of available therapeutic Most recently, there has been a substantial buzz Toptions that is now almost as diverse as this group around the idea of genetically engineering T cells of tumors. Immunotherapy in particular is front and before they are reintroduced into the patient, to center in the battle to control these diseases. Here, increase their anti-tumor efficacy and minimize we describe the latest promising developments. damage to healthy tissue. This is achieved either by manipulating the antigen binding portion of the Exploiting T cells T-cell receptor to alter its specificity (TCR T cells) The treatment landscape for hematologic malig- or by generating artificial fusion receptors known as nancies is diverse, but one particular type of therapy chimeric antigen receptors (CAR T cells; Figure 1). has led the charge in improving patient outcomes. The former is limited by the need for the TCR to be Several features of hematologic malignancies may genetically matched to the patient’s immune type, make them particularly amenable to immunother- whereas the latter is more flexible in this regard and apy, including the fact that they are derived from has proved most successful. corrupt immune cells and come into constant con- CARs are formed by fusing part of the single- tact with other immune cells within the hemato- chain variable fragment of a monoclonal antibody poietic environment in which they reside.
    [Show full text]
  • New Additions to Antibody Panels in the Characterisation of Chronic Lymphoproliferative Disorders J Clin Pathol: First Published As on 1 March 2002
    180 REVIEW New additions to antibody panels in the characterisation of chronic lymphoproliferative disorders J Clin Pathol: first published as on 1 March 2002. Downloaded from E Matutes ............................................................................................................................. J Clin Pathol 2002;55:180–183 Advances in flow cytometry techniques and the In addition to the panel of monoclonal antibod- availability of monoclonal antibodies that detect key ies routinely used in the past decade,2 and recom- mended in 1994 by the general haematology task functional molecules on lymphocytes have contributed force of the British Committee for Standards in greatly to a more precise diagnosis of the chronic Haematology,3 several others have been shown to lymphoproliferative disorders. In addition to the provide relevant diagnostic and/or prognostic information, and could be incorporated into the diagnostic value, the expression of certain markers such panel of markers in a routine practice. The as p53 or CD38 provides relevant prognostic characteristics of these monoclonal antibodies information to the clinician. Beyond their diagnostic and and the molecules that they recognise, in addition to their relevance for the characterisation of the prognostic value, immunological markers play a major chronic lymphoproliferative disorders, are de- role in the detection of minimal residual disease, scribed below enabling the clinician to estimate more accurately the response to chemotherapy. Those monoclonal MONOCLONAL ANTIBODIES TO CD79B CD79 is a heterodimeric molecule comprising two antibodies that are relevant to the characterisation of the polypeptide chains: the α-chain or mb1 (CD79a) chronic lymphoproliferative disorders and that could be and the β-chain or B29 (CD79b). CD79b is incorporated in a routine practice are discussed.
    [Show full text]
  • Predictive Significance of the Cut-Off Value of CD20 Expression in Patients with B-Cell Lymphoma
    1101-1107.qxd 25/8/2010 12:26 ÌÌ ™ÂÏ›‰·1101 ONCOLOGY REPORTS 24: 1101-1107, 2010 Predictive significance of the cut-off value of CD20 expression in patients with B-cell lymphoma MATEJA HORVAT1, VERONIKA KLOBOVES PREVODNIK2, JAKA LAVRENCAK2 and BARBARA JEZERSEK NOVAKOVIC3 1Bayer d.o.o., Bravnicarjeva 13; Departments of 2Cytopathology, 3Medical Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000 Ljubljana, Slovenia Received May 25, 2010; Accepted July 15, 2010 DOI: 10.3892/or_00000961 Abstract. The introduction of the anti-CD20 monoclonal 0.5667; 95%CI, 0.124 to 3.18, p=0.57]. Even though we have antibody, rituximab, into the treatment of patients with B-cell proved that patients with a CD20 expression level above the lymphomas has improved the overall response rate, as well as cut-off value treated with rituximab had a significantly longer the response duration and the overall survival of these patients. OS [hazard ratio (HR), 0.4573; 95%CI, 0.1364 to 0.9461, However, only a few studies have addressed the question of p=0.0383] than patients with a CD20 expression level below whether higher CD20 expression parallels with better treatment the cut-off value. Among our study population, 17.5% had a outcomes. The aim of this study was to assess the relationship CD20 expression level below the cut-off value. The highest between the level of CD20 expression and overall survival percentage (80%) of the patients with a CD20 expression (OS), disease-free survival (DFS) along with the overall level below the cut-off value belonged to the group of chronic response rate (ORR) in B-cell lymphoma patients.
    [Show full text]