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International Journal of Cell Cloning Nov 1987This paper describes a culture system which supports the formation of B cell and some T cell colonies under serum-free conditions in peripheral blood samples of normal... (Comparative Study)
Comparative Study
This paper describes a culture system which supports the formation of B cell and some T cell colonies under serum-free conditions in peripheral blood samples of normal individuals and patients with chronic lymphocytic leukemia (CLL) of B cell type. In this system, serum is replaced by bovine serum albumin, transferrin, cholesterol, insulin and catalase or horseradish peroxidase. In addition, it is necessary to add staphylococcus protein A, mitomycin-treated T cells as feeders and phytohemagglutinin leukocyte-conditioned medium as a source of growth factors. The plating efficiency is greatly enhanced when normal cells are incubated with galactose oxidase prior to plating and when CLL cells are exposed sequentially to neuraminidase and galactose oxidase.
Topics: B-Lymphocytes; Cells, Cultured; Culture Media; Culture Techniques; Humans; Leukemia, Lymphoid; Mitomycin; Mitomycins; Reference Values; T-Lymphocytes
PubMed: 3123561
DOI: 10.1002/stem.5530050606 -
Blood Feb 2012The chemokine receptor CXCR4, which normally regulates stromal stem cell interactions in the bone marrow, is highly expressed on a variety of malignant hematologic...
The chemokine receptor CXCR4, which normally regulates stromal stem cell interactions in the bone marrow, is highly expressed on a variety of malignant hematologic cells, including lymphoma and lymphocytic leukemias. A new treatment concept has arisen wherein CXCR4 may be an effective therapeutic target as an adjunct to treatment of hematologic neoplasms with chemo- and immunotherapy. In the present study, we developed pepducins, cell-penetrating lipopeptide antagonists of CXCR4, to interdict CXCL12-CXCR4 transmembrane signaling to intracellular G-proteins. We demonstrate that pepducins targeting the first (i1) or third (i3) intracellular loops of CXCR4 completely abrogate CXCL12-mediated cell migration of lymphocytic leukemias and lymphomas. Stromal-cell coculture protects lymphoma cells from apoptosis in response to treatment with the CD20-targeted Ab rituximab. However, combination treatment with CXCR4 pepducins and rituximab significantly increases the apoptotic effect of rituximab. Furthermore, treatment of mice bearing disseminated lymphoma xenografts with pepducins alone or in combination with rituximab significantly increased their survival. These data demonstrate that CXCL12-CXCR4 signaling can be effectively inhibited by cell-penetrating pepducins, which represents a potential new treatment strategy for lymphoid malignancies.
Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Drug Delivery Systems; Female; Humans; Interleukin Receptor Common gamma Subunit; Leukemia, Lymphoid; Lipopeptides; Lymphoma; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Models, Molecular; Molecular Targeted Therapy; Receptors, CXCR4; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
PubMed: 22186993
DOI: 10.1182/blood-2011-04-347518 -
Blood Nov 2005Activating mutations in tyrosine kinases have been identified in hematopoietic and nonhematopoietic malignancies. Recently, we and others identified a single recurrent... (Clinical Trial)
Clinical Trial
The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia.
Activating mutations in tyrosine kinases have been identified in hematopoietic and nonhematopoietic malignancies. Recently, we and others identified a single recurrent somatic activating mutation (JAK2V617F) in the Janus kinase 2 (JAK2) tyrosine kinase in the myeloproliferative disorders (MPDs) polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. We used direct sequence analysis to determine if the JAK2V617F mutation was present in acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML)/atypical chronic myelogenous leukemia (aCML), myelodysplastic syndrome (MDS), B-lineage acute lymphoblastic leukemia (ALL), T-cell ALL, and chronic lymphocytic leukemia (CLL). Analysis of 222 patients with AML identified JAK2V617F mutations in 4 patients with AML, 3 of whom had a preceding MPD. JAK2V617F mutations were identified in 9 (7.8%) of 116 CMML/a CML samples, and in 2 (4.2%) of 48 MDS samples. We did not identify the JAK2V617F disease allele in B-lineage ALL (n = 83), T-cell ALL (n = 93), or CLL (n = 45). These data indicate that the JAK2V617F allele is present in acute and chronic myeloid malignancies but not in lymphoid malignancies.
Topics: Aged; Alleles; Amino Acid Substitution; Case-Control Studies; Enzyme Activation; Female; Humans; Janus Kinase 2; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Male; Middle Aged; Point Mutation; Protein-Tyrosine Kinases; Proto-Oncogene Proteins
PubMed: 16081687
DOI: 10.1182/blood-2005-05-1898 -
Blood Jan 1985Fifty-five patients with a clonal expansion of B lymphocytes in the peripheral blood were studied. According to the Kiel classification, 22 patients had chronic...
Fifty-five patients with a clonal expansion of B lymphocytes in the peripheral blood were studied. According to the Kiel classification, 22 patients had chronic lymphocytic leukemia (CLL), 29 had immunocytoma (IC), two had prolymphocytic leukemia, and one had centrocytic lymphoma; one was not subclassified. Cytogenetic studies after B cell mitogen stimulation showed that six patients had an extra chromosome 12 as the sole abnormality. Another ten patients had an extra chromosome 12 together with other abnormalities. One patient had dup(12). Fifteen patients showed clonal aberrations without +12. Eleven patients showed only normal metaphases, and 12 patients were not evaluated cytogenetically. The cytogenetic subgroup pattern did not distinguish between CLL and IC patients. There was no significant difference between the CLL and IC groups as regards clinical findings and prognosis. However, the cytogenetic typing proved to be of prognostic significance. Increasing numbers of chromosomal aberrations within the cell clone were significantly associated with a poorer prognosis, ie, with impairment of survival (P = .04) and therapy-free survival (P less than 10(-4]. Patients with complex karyotypes (at least clonal aberrations) showed the poorest survival (P = .007). Patients with +12 required treatment earlier than patients with a normal karyotype (P = .01) and patients with karyotypic changes other than +12 (P = .006). These latter differences were even more pronounced when only IC patients were considered (P = .005 and P = .002, respectively). A multivariate analysis revealed that +12 was as strong an indicator of poor survival as advanced Rai or Binet stages and a stronger predictor of therapy-demanding disease.
Topics: Adult; Aged; B-Lymphocytes; Chromosome Aberrations; Female; Humans; Karyotyping; Leukemia, Lymphoid; Lymphoma; Male; Middle Aged; Prognosis
PubMed: 3871161
DOI: No ID Found -
Acta Clinica Croatica Jun 2018T-cell large granular lymphocytic leukemia (T-LGLL) is an uncommon but probably underdiagnosed disease caused by clonal proliferation of large granular lymphocytes....
T-cell large granular lymphocytic leukemia (T-LGLL) is an uncommon but probably underdiagnosed disease caused by clonal proliferation of large granular lymphocytes. Diagnosis is typically based on the high number of morphologically characteristic lymphoid cells and finding of an abnormal immunophenotype by flow cytometry. Because of its relatively indolent clinical behavior, observation is often an appropriate therapy. Here we present a case of a 53-year-old male admitted to the hospital because of abdominal pain. Blood examination revealed mild mycrocitic anemia and multiplied lactate dehydrogenase level. Abdominal ultrasound showed splenomegaly of 16 cm, with no lymphadenopathy. Fine needle aspiration of bone marrow revealed hypocellular marrow with 50% of atypical lymphoid cells. There were 81% of atypical medium sized granular lymphocytes with irregularly shaped nuclei in peripheral blood, so the cytologic diagnosis was lymphoproliferative process. Bone marrow biopsy showed nodular and interstitial proliferation of small, partially atypical T lymphocytic cells positive for CD2, CD3, CD5, CD8, granzyme and TIA, and negative for hairy cell markers, CD10, MUM 1, bcl 1, CD4 and CD56. The finding was consistent with T-LGLL. Due to splenomegaly, the patient was treated with cyclosporine and gradually reduced dose of corticosteroids, leading to regression of splenomegaly and normalization of lactate dehydrogenase level.
Topics: Anemia; Flow Cytometry; Humans; Immunophenotyping; Leukemia, Large Granular Lymphocytic; Lymphocytes; Male; Middle Aged
PubMed: 30431731
DOI: 10.20471/acc.2018.57.02.18 -
Journal of the American Veterinary... Dec 2014Severe lymphocytosis and leukocytosis were detected during examination of a 10-year-old sexually intact male bat-eared fox (Otocyon megalotis) with regionally extensive...
CASE DESCRIPTION
Severe lymphocytosis and leukocytosis were detected during examination of a 10-year-old sexually intact male bat-eared fox (Otocyon megalotis) with regionally extensive alopecia.
CLINICAL FINDINGS
A CBC revealed severe leukocytosis (39,100 leukocytes/μL) and marked lymphocytosis (90%). A blood smear consisted predominantly of intermediate-sized lymphocytes and few large lymphocytes, with mild to moderate nuclear atypia. These findings were highly suggestive of chronic lymphocytic leukemia (CLL). Cytologic evaluation of bone marrow aspirates revealed no evidence of overt malignancy, with 10% of all cells identified as small to intermediate-sized mature lymphocytes.
TREATMENT AND OUTCOME
Treatment with chlorambucil and prednisone administered orally over a 1.8-year period decreased the leukocyte and lymphocyte counts to within reference intervals with no adverse effects. Although repeated flow cytometry revealed evidence of residual disease, the fox remained free of clinical disease, and WBC counts were within reference intervals for this species. At 22 months after initial evaluation, the fox was euthanized because of debilitating arthritis. No evidence of CLL was detected grossly or histologically during necropsy.
CLINICAL RELEVANCE
To the authors' knowledge, this was the first report of CLL in a bat-eared fox and first successful treatment in a nondomestic carnivore. Treatment in accordance with a chemotherapeutic protocol successfully resolved the leukocytosis and lymphocytosis with no serious adverse effects. Description of this fox and the treatment protocol should provide a valuable reference for future cases in this and other nondomestic canine species.
Topics: Animals; Animals, Zoo; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Chlorambucil; Foxes; Leukemia, Lymphoid; Male; Prednisone
PubMed: 25459484
DOI: 10.2460/javma.245.12.1391 -
Blood Jan 1980Leukemic cells from 20 patients with chronic lymphocytic leukemia (CLL) and 60 patients with acute lymphocytic leukemia (ALL) were studied for T- and B-lymphocyte cell...
Leukemic cells from 20 patients with chronic lymphocytic leukemia (CLL) and 60 patients with acute lymphocytic leukemia (ALL) were studied for T- and B-lymphocyte cell surface membrane markers. B-cell markers included surface membrane immunoglobulin, erythrocyte-antibody complement rosette formation, and B-cell (a-like or HLA-DR) antigens detected by a B-cell antiserum. T-cell markers included spontaneous sheep red blood cell rosette formation and a cytotoxic reaction to a specific T-cell antiserum. Seven patients with CLL and two with ALL had dual B and T markers. We propose that dual B- and T-cell markers are more common in CLL and ALL patients than previously reported. With newer and more sensitive tests for identification of B and T cells, this observation may be recognized more frequently.
Topics: Absorption; Animals; Antibody Specificity; Antilymphocyte Serum; B-Lymphocytes; Humans; Leukemia, Lymphoid; Rabbits; Receptors, Antigen, B-Cell; Receptors, Complement; Receptors, Fc; Sheep; T-Lymphocytes
PubMed: 6965347
DOI: No ID Found -
Blood Oct 1983Neoplastic populations from 25 cases of B-lymphocytic leukemia (B-LL) were investigated in an attempt to define the stages of maturation arrest represented in this...
Phenotypes in chronic B-lymphocytic leukemia probed by monoclonal antibodies and immunoglobulin secretion studies: identification of stages of maturation arrest and the relation to clinical findings.
Neoplastic populations from 25 cases of B-lymphocytic leukemia (B-LL) were investigated in an attempt to define the stages of maturation arrest represented in this disease and the relationship, if any, to various clinical parameters. Intrinsic to this study was the expression of a number of B-cell antigens defined by monoclonal antibodies. These included antibodies to B1 and B2, both expressed exclusively on B lymphocytes, but with the latter probably restricted to a narrow window of differentiation, BB-1 and LB-1, both markers of activated lymphocytes, and 38.13, a monoclonal antibody raised against and recognizing an epitope expressed on Burkitt lymphoma cells. While the patterns of reactivities were complex, the cases could be classified into various groups on the basis of the phenotypes revealed. These were termed "pre-B," "early-B," "intermediate-B," "mature-B," and "secretory-B" from their patterns of immunoglobulin (Ig) isotype expression and their capacity to secrete Ig in short-term culture. Although B1 was detected on neoplastic cells from all but one case, its intensity of expression varied markedly, being strongest on the "mature-B" and "secretory-B" cases and weakest on the "pre-B" type. The expression of B2 was essentially restricted to the "intermediate-B," "mature-B," and "secretory-B" cases and was usually, but not invariably, accompanied by the coexpression of surface IgM and IgD. While expression of BB-1 was restricted to a few cases with mature features, LB-1 was more frequently detected and found predominantly on "intermediate-B" and "mature-B" cases. The 38.13 antibody was found to react weakly with a number of the populations coexpressing IgM and IgD. The export of large amounts of whole Ig was restricted to three "secretory-B" cases all of which were associated with a serum M-component corresponding to the Ig isotype secreted in vitro. In contrast, the secretion of free Ig light chains was a consistent feature of all B-LL, and the amounts detected did not vary considerably between the different types. No correlation between immunologic cell-type and the stage of the disease was apparent. Classification of the cases into "true" B-chronic lymphocytic leukemia and immunocytoma similarly revealed no strict association of these histopathologic entities with any particular phenotypic group, although those cases with the more mature features tended to be immunocytomas. The findings are discussed within the context of normal B-cell differentiation pathways.
Topics: Antibodies, Monoclonal; B-Lymphocytes; Cell Differentiation; Humans; Immunoglobulin M; Leukemia, Lymphoid; Phenotype
PubMed: 6603884
DOI: No ID Found -
British Journal of Haematology Apr 1999
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Chronic lymphocytic leukaemia and prolymphocytic leukaemia. Two coins or two sides of the same coin?Haematologica Sep 2020
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Numismatics
PubMed: 33054069
DOI: 10.3324/haematol.2020.253062