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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We show that a highly aggressive subclone of murine BCL-1 B-lineage leukemia expresses a single 2.4-kb transcript hybridizing to the human CD19 cDNA probe and reacts strongly with the anti-human CD19 monoclonal antibodies (MoAb) B43, B4, Leu-12, and J3-119. In contrast to their strong reactivity with anti-human CD19 MoAb, BCL-1 cells show no reactivity with MoAb directed against human CD22, CD72, HLA-DR, IgD, or IgM. Western blot analysis of BCL-1 whole cell lysates with the anti-human CD19 MoAb J3-119 showed a single 69-Kd protein band, which was not detected by the negative control MoAb G19.4 (anti-CD3). In contrast to BCL-1 cells, normal BALB/c splenocytes or mouse splenocyte/myeloma hybridoma cell lines did not (1) express any transcripts that hybridized to the human CD19 cDNA probe, (2) react with B43/anti-CD19 MoAb, or (3) express the 69-Kd protein that reacts with the anti-human CD19 MoAb J3-119. Murine BCL-1 B-cell leukemia thus provides a unique model of disseminated B-lineage leukemia to evaluate the antileukemic efficacy of anti-CD19 immunotoxins. This model was subsequently used to evaluate the in vivo homing ability, pharmacokinetics, and antileukemic efficacy of B43 MoAb conjugated to the plant hemitoxin pokeweed antiviral protein (PAP). B43-PAP immunotoxin (1) showed strong and antigen-specific reactivity with BCL-1 cells, (2) promptly penetrated the spleens of leukemic mice, (3) rapidly reduced the BCL-1 leukemia burden of leukemic mice and, most importantly, (4) improved survival. Finally, B43-PAP immunotoxin was more effective against BCL-1 leukemia than 700 cGy (LD100/30) total body irradiation (TBI) followed by syngeneic bone marrow transplantation (BMT).
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PMID:In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin against BCL-1 murine B-cell leukemia. 137 9

Rare subpopulations of normal marrow B lymphoid cells expressing immunophenotypes typically found in B-lineage acute lymphoblastic leukaemias (ALL) were sought by multiparameter flow cytometry. First, CD34+ marrow leukocytes were isolated by immune adherence using immunomagnetic microspheres, and analyzed for coexpression of the following pairs of membrane antigens: CD34 CD22; CD34 CD20; and CD10 CD22. Terminal deoxynucleotidyl transferase expression was not assessed. All three antigen combinations were found on small percentages of the CD34-enriched cell population. Second, unseparated normal low density marrow leukocytes were examined by 'gating' on cells with the right-angle light scatter of lymphoid cells, plus either CD34+ or CD10+ immunofluorescence. This independent approach confirmed that rare subsets of normal cells coexpress 'immature' and 'mature' differentiation antigens. In addition, remission marrow cells were examined from two children who had completed therapy for ALL two and four months earlier. Both specimens had a more than threefold increase in CD34+ cells over normal marrow, and cells coexpressing immature and mature cell surface antigens were easily detected. These findings demonstrate that immunophenotypes characteristic of B-lineage ALL, previously labeled 'asynchronous' with respect to the developmental sequence of the majority of normal B lymphoid cells, exist at low frequency in normal human bone marrow.
Leukemia 1992 Apr
PMID:Flow cytometric detection of rare normal human marrow cells with immunophenotypes characteristic of acute lymphoblastic leukemia cells. 137 1

The clinical utility of the indirect immunofluorescence (IF) and the alkaline phosphatase-anti-alkaline phosphatase (APAAP) techniques was compared in 103 newly diagnosed acute leukaemia patients immunophenotyped using a panel of 19 monoclonal antibodies (MoAb). In spite of slight variations in the percentages of cells reacting with particular MoAbs when comparing the two methods we found no discrepancies in the final classification of each case. In ANLL (n = 73) the best correlation between the two methods was found for CDw65 which is a good screening marker, and for CD15 having a prognostic significance. In ALL (n = 30) the best correlation was observed for CD19 and CD10, both of great diagnostic importance. The following antigens present both in membrane and in cytoplasm displayed higher positivity with the APAAP than in IF HLA-Dr, CD71 and CD11b in ANLL, CD22 and HLA-Dr in nonT-ALL and CD3 in T-ALL. The important advantages of the APAAP technique are: 1) its use with routinely performed bone marrow or peripheral blood films, which can be stored before staining, 2) the possibility of correlating morphology with immunological characterization and documentation of the results.
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PMID:[Comparison of clinical usefulness of immunophenotyping of leukemia using the immunofluorescence and immunoenzyme APAAP methods]. 148 65

Monoclonal antibodies (mAbs) of IPO series were developed following immunization with human B cell lines RPMI-1788, Daudi, and spleen cells from a patient with hairy cell leukemia. Reactivity of these mAbs was studied on 19 human cell lines, mononuclear cells of 50 healthy persons and 142 patients with leukemias and lymphomas. It was shown that mAbs IPO-3, IPO-10 and IPO-24 define B cell-specific antigens expressed at different stages of maturation. MAb IPO-3 reacted with activated B lymphocytes. MAb IPO-10 defined the antigen which appears on B cell progenitors following HLA-DR and proceeding CD19, CD10, CD22, CD37; cy mu and CD20 and have been lost during terminal differentiation. The antigen detected by mAb IPO-24 was expressed throughout B cell ontogeny from pre-B cell until the B-blasts. MAb IPO-4 detected an antigen of activated T and B lymphocytes. These mAbs are useful tools in the leukemia and lymphoma phenotypic characterization and classification.
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PMID:Monoclonal antibodies of IPO series against B cell differentiation antigens in leukemia and lymphoma immunophenotyping. 152 2

We studied the blasts from 795 children greater than 1 year of age with newly diagnosed, untreated B-precursor acute lymphoblastic leukemia (ALL) for expression of the hematopoietic stem cell-associated antigen CD34. All cases were confirmed as B-lineage lymphoblastic leukemia by virtue of expression of CD19 and/or CD22, lack of T-cell antigens, and lack of surface-membrane immunoglobulin (Ig). The CD34 antigen was present in at least 10% of blast cells in 587 (73.8%) of the patients. There was no significant difference in presenting clinical characteristics between CD34+ and CD34- patients save for an increased incidence of CNS involvement at diagnosis in the latter. Patients with CD34+ leukemia were more likely to have blasts expressing CD22, CD9, and CD13 antigens but were less likely to coexpress CD20. Patients with pre-B (cytoplasmic mu) ALL were significantly more likely to lack CD34 on their blasts, while children with hyperdiploid ALL were more likely to be CD34+. Although remission induction rates were not significantly different between patients with CD34+ and CD34-ALL (P = .23), event-free survival was shorter for patients with CD34- leukemia (P = .0014). Even though CD34 expression was associated with certain other known prognostically favorable variables including hyperdiploidy and lack of cytoplasmic Ig, it had an independent favorable effect on treatment outcome, even after adjusting for competing prognostic factors.
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PMID:Prognostic significance of CD34 expression in childhood B-precursor acute lymphocytic leukemia: a Pediatric Oncology Group study. 169 10

Maturation of adult human bone marrow (BM) B cells is accompanied by the sequential acquisition and loss of characteristic cell surface antigens (Loken et al., Blood 70:1316). Little is known about these changes in fetal BM B cells. In order to compare fetal with adult B cell development, we performed three-color, flow cytometric analyses of cell surface antigens, as well as nuclear TdT staining, on lymphoid cells from fetal BM. Mononuclear cells isolated from fetal BM (18-22 weeks) were stained with combinations of antibodies against CD3, CD10, CD19, CD20, CD21, CD22, CD34, CD45, PCA-1, IgM, and HLA-DR. Analysis of six separate fetal BM specimens indicated that combinations of cell surface antigens were expressed on analogous populations in fetal and adult BM. Consistent with adult BM, greater than 95% of TdT+ cells within the CD10+ population were CD34+, whereas less than 5% were CD34-. This CD10+/CD34+/TdT+ population constituted 30-40% of the total B cell compartment, compared with 10% in adults. Quantitative changes in CD45 expression on fetal BM B cells defined three clear populations, as has been observed in adults. In striking contrast to adult BM, greater than 95% of CD19+ and greater than 95% of surface IgM+ cells were CD10+, indicating that CD10 is a pan-B cell antigen in fetal BM. Virtually no mature B cells expressing CD21, CD22, or PCA-1 were detected in fetal BM. Our results indicate a preponderance of immature phenotypes exist in the fetal BM B cell compartment. These immature cells can be grouped into three distinct populations, and probably correspond to expanded populations found less frequently in adult BM. This striking increase in the earliest identifiable stages of B cell ontogeny is consistent with an active expansion of cells destined to constitute the humoral immune system during fetal development.
Leukemia 1990 May
PMID:Multiparameter flow cytometric analysis of human fetal bone marrow B cells. 169 9

A panel of monoclonal antibodies (mAbs) directed against B-cell and hairy cell leukaemia (HCL)-associated antigens was used to identify residual hairy cells in the peripheral blood and/or bone marrow samples from 20 patients with HCL, following treatment with interferon-alpha (IFN-alpha) or interferon-beta (IFN-beta). In all cases, hairy cells retained their characteristic phenotype, e.g. positivity for CD22, CD11c, CD25, CD32, and the HCL-associated trimeric protein (t-GP) recognized by the mAbs HML-1, B-ly7, LF61 and Ber-Act8. The most specific marker for identifying a small percentage of hairy cells in peripheral blood cytospins, was t-GP. In alkaline phosphatase/anti alkaline phosphatase (APAAP) stained preparations, t-GP+ hairy cells (provided with large cytoplasm and hairy surface) could be usually distinguished from t-GP+ normal lymphocytes (small-sized cells with smooth surface). In doubtful cases the percentage of residual hairy cells could exactly be estimated by double immunofluorescence staining for CD22 (B-cell marker) and t-GP. The rationale of the test is based on the finding that the small percentage (about 1%) of t-GP+ lymphocytes circulating in the peripheral blood of normal individuals are T-cells of the CD8 subset and not B-cells. The best markers for identifying residual hairy cells in routine bone marrow biopsies were CD45RA (mAb 4KB5) and CD20 (mAb L26). Immunohistological labelling was superior to morphological examination in picking up scattered hairy cells in bone marrow biopsies showing either severe hypoplasia or exuberant hyperplasia of normal haemopoietic series.
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PMID:Selection of a panel of monoclonal antibodies for monitoring residual disease in peripheral blood and bone marrow of interferon-treated hairy cell leukaemia patients. 170 9

Detailed immunophenotypic analyses of immunologically classified leukemias and lymphomas showed that CD40 displays an exquisite B-lineage specificity within the human lymphopoietic system. Notably, 82% of B-lineage chronic lymphocytic leukemias (CLLs), 82% of B-lineage hairy cell leukemias (HCLs), 86% of B-lineage non-Hodgkin's lymphomas (NHLs), and 29% of B-lineage acute lymphoblastic leukemias (ALLs) were CD40+. Quantitative analyses of the correlated expression of CD40 and other B-lineage differentiation antigens on fetal lymphoid precursor cells by multiparameter two-color/three-color flow cytometry, combined with analyses of sequential antigen expression on fluorescence-activated cell fluorescence activated cell sorter (FACS) isolated immunologically distinct fetal B-cell precursor subpopulations during in vitro proliferation and differentiation, provided evidence that the acquisition of CD40 antigen in human B-cell ontogeny occurs subsequent to the expression of CD10 and CD19 antigens but before the surface expression of CD20, CD21, CD22, CD24, and surface immunoglobulin M (sIgM). Some leukemic pro-B cells from ALL patients as well as normal pro-B cell clones from fetal livers displaying germline Ig heavy chain genes were CD40+, indicating that the acquisition of CD40 antigen likely precedes the rearrangement of Ig heavy chain genes. CD40+ FACS-sorted malignant cells from B-lineage ALL as well as B-lineage NHL patients were capable of in vitro clonogenic growth, indicating the CD40 antigen is expressed on clonogenic leukemia and lymphoma cells. This hypothesis was confirmed by the ability of an anti-CD40 immunotoxin that we used as an antigen-specific cytotoxic probe to effectively kill clonogenic B-lineage ALL and NHL cells.
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PMID:Temporal association of CD40 antigen expression with discrete stages of human B-cell ontogeny and the efficacy of anti-CD40 immunotoxins against clonogenic B-lineage acute lymphoblastic leukemia as well as B-lineage non-Hodgkin's lymphoma cells. 170 26

B-precursor acute lymphoblastic leukemia bone marrow specimens that contained subpopulations of cells with immunophenotypes corresponding to early (CD34) and late (CD20) and (CD22) stages of normal B-cell differentiation were studied. Subpopulations of cells were isolated according to immunophenotype and then analyzed by both a clonogenic assay and molecular genetic methods. Clonal equivalence of the early and late immunophenotypic subpopulations was confirmed for each case by the demonstration of identical lg gene rearrangements. The in vitro colony-forming assay consistently showed a growth advantage for the CD34+ subpopulations over the CD34- subpopulations. CD34 mRNA was detected readily in these isolated precursor cells. When two specimens in which virtually all of the leukemia cells were CD34+ and CD34+CD20+ and CD34+CD22+ subpopulations were also present the CD34 mRNA was limited to the cells without the late-stage differentiation antigens on their surface. Furthermore, the c-myb mRNA was found only in the subpopulations that also contained CD34 mRNA. Our results show that a limited program of differentiation reminiscent of normal B-cell development may be present in this leukemia.
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PMID:Differentiation in B-precursor acute lymphoblastic leukemia cell populations with CD34-positive subpopulations. 171 8

We show here that analysis of VpreB gene transcription can be a specific way to identify acute leukemias of cells at very early stages of B-cell development. Northern blot analysis of RNAs from 63 leukemia samples showed that VpreB RNA was present in malignancies of precursor B cells, the expression being a feature of both common acute lymphoblastic leukemia (ALL) (CD10+) and null ALL (CD10-). It was absent from malignancies of mature B cells (surface Ig positive), from acute leukemias of the T-cell lineage and granulocyte-macrophage lineages, and from normal tonsil B and T lymphocytes. Chronic myeloid leukemia blast crises of the B-precursor-cell type expressed the VpreB gene while myeloid blast crises did not. VpreB RNA was also expressed in the neoplastic cells of one of three patients with acute undifferentiated leukemias. These data show that VpreB RNA expression is a marker of the malignant forms of precursor B cells, and that it appears at least as early as cytoplasmic CD22 and CD19 in tumors of the B-cell lineage.
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PMID:VpreB gene expression in hematopoietic malignancies: a lineage- and stage-restricted marker for B-cell precursor leukemias. 188 24


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