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

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

In the present study, two isotype-matching mAb, SN5d and SN5, which are directed toward two distinctively different epitopes of common acute lymphoblastic leukemia Ag (CD10) but show a very similar binding affinity to leukemia cells, were compared for their in vivo antitumor activity after conjugated to ricin A chain (RA). Our recently established nude mouse model carrying an ascitic tumor of NALM-6 human pre-B leukemia cells was used as the tumor model. A marked difference was observed in the in vivo antitumor efficacy between SN5d-RA and SN5-RA; SN5d-RA was much more effective than SN5-RA. Several experiments were carried out to gain information concerning the mechanisms involved in the different antitumor efficacy of the two immunotoxins. Although naked (unconjugated) mAb SN5d was much less effective than SN5d-RA conjugates in the in vivo tumor suppression, mAb SN5d was more effective than mAb SN5 in the in vivo tumor suppression. Additionally, marked differences were found between SN5d and SN5 in the induction of antigenic modulation and in the regulation of Ag biosynthesis and expression. Binding of SN5 to NALM-6 leukemia cells caused strong antigenic modulation (down-regulation of Ag expression) and strongly down-regulated Ag biosynthesis and cell surface expression of new Ag. In contrast, binding of SN5d to NALM-6 leukemia cells caused little modulation of overall cell surface expression of common acute lymphoblastic leukemia Ag; the decrease of old Ag by endocytosis after binding to mAb SN5d was compensated by newly exocytosed cell-surface expressed Ag. The present results appear to reveal a novel mechanism which regulates cytotoxic activities of antibodies and immunoconjugates.
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PMID:Marked difference in the in vivo antitumor efficacy between two immunotoxins targeted to different epitopes of common acute lymphoblastic leukemia antigen (CD10). Mechanisms involved in the differential activities of immunotoxins. 169 14

The antigen CD10 (common acute lymphoblastic leukaemia antigen), which is the zinc metalloprotease, neutral endopeptidase 24.11 (also known as NEP or 'enkephalinase'), is expressed by acute lymphoblastic leukaemias, normal lymphoid progenitors, mature polymorphonuclear leukocytes and certain nonhaematopoietic cells. CD10/NEP hydrolyses several naturally occurring peptides, including the endogenous opioid pentapeptides Met- and Leu-enkephalin. In invertebrate organisms such as the mollusc Mytilus edulis, Met-enkephalin triggers inflammatory responses by inducing morphological changes, directed migration and aggregation of haemocytes. We report here that a structure related to CD10/NEP is expressed by M. edulis haemocytes and that abrogation of CD10/NEP enzymatic activity reduces the amount of Met-enkephalin required for haemocyte activation by five orders of magnitude. Similar results are obtained with CD10+ human polymorphonuclear leukocytes, indicating that CD10/NEP related structures regulate enkephalin-mediated inflammatory responses in organisms whose ancestors diverged approximately 500 million years ago.
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PMID:Downregulation of enkephalin-mediated inflammatory responses by CD10/neutral endopeptidase 24.11. 169 30

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

The expression of myeloid antigens has been extensively examined using two-color analysis in 43 children with B-lineage acute lymphoblastic leukemia (ALL). On pre-culture cells, CD33 expression was frequently observed in CD19+, CD10- B-precursor ALL, and CD14 was expressed only on the cells from B-precursor ALL expressing CD19, CD10 and CD20, and B-ALL. After 2 or 3 days of culture without TPA, CD13 emerged on the cells from 21 of 29 patients irrespective of the presence or the absence of fetal calf serum in the culture. Of four patients with CD10+ B-precursor ALL, which showed no expression of CD13 after culture, two had T-cell associated antigens. Whereas the addition of TPA to the culture enhanced the expression of CD13 on the cells from acute non-lymphocytic leukemia (ANLL), TPA reduced the expression of this antigen on B-precursor cells. These findings suggest that the regulatory mechanism of CD13 expression may be different between B-precursor ALL and ANLL. Co-culture with cycloheximide mostly abrogated the induction of CD13, suggesting that CD13 expression was mainly dependent on de novo protein synthesis.
Leukemia 1991 Jan
PMID:In vivo and in vitro expression of myeloid antigens on B-lineage acute lymphoblastic leukemia cells. 170 35

CD34 is a 110-kD glycoprotein previously shown by a variety of monoclonal antibodies (MoAbs) to be expressed selectively on immature hematopoietic cells. However, more detailed characterization of CD34+ cells has been hampered by lack of anti-CD34 MoAbs that can be labelled directly with fluorochromes to facilitate subpopulation analysis by multi-parameter flow cytometry. We have recently isolated a murine anti-CD34 MoAb, designated as 8G12, that can be directly labelled with fluorochromes such as FITC. In this study, we have exploited this property of 8G12 to compare the reactivity of 8G12 and My10 with normal and leukaemic human marrow cells and to characterize normal early human B cell precursors by two- and three-colour immunofluorescence analysis. Comparison of three-colour staining profiles of normal bone marrow cells incubated with both 8G12 and MY10, and either anti-CD10 or anti-CD19 MoAb revealed the reactivity patterns of 8G12 and MY10 to be indistinguishable. This conclusion was confirmed by a similar comparative analysis of 8G12 and MY10 staining of blood and bone marrow cells from 4 patients with B lineage acute lymphoblastic leukaemia (ALL). Of interest, both 8G12 and MY10 detected a CD34+CD10+CD19- population in normal adult bone marrow. To determine whether a CD34+CD10+CD19- precursor population previously reported by others to exist in fetal liver could also be identified, CD10+CD16- marrow cells were first isolated by FACS and the sorted cells then re-analysed for expression of CD19 and CD34. These studies showed that all of the sorted CD10+ cells that expressed CD34 appeared to coexpress CD19. No CD34+CD10+CD19- cells were detected (at a sensitivity of less than or equal to 0.1%). Further studies will be required to determine whether a very minor population of CD34+CD10+CD19- cells may still be generated in the normal development of B cells in adult human marrow.
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PMID:Expression of CD34 on human B cell precursors. 171 82

Of 14 patients who underwent allogeneic or syngeneic bone marrow transplantation, 6 had a transient appearance of small blastoid cells in the bone marrow after transplantation. Most of these patients (11) had leukemia, although 3 had severe aplastic anemia. The cells were 8-18 micron in diameter and had scant cytoplasm and dense nuclei with smooth, homogeneous chromatin. They often had distinct nuclear clefts. These cells constituted 4.0-21.3% of the total number of bone marrow cells. They were not reactive with peroxidase, alpha-naphtyl butylate esterase, naphthol AS-D chloroacetate esterase, or periodic acid-Schiff stains. Immunocytochemical analysis revealed that the small blastoid cells expressed terminal deoxynucleotidyl transferase, Ia-like, CD19, and CD10 antigens and cytoplasmic mu heavy chains, indicating a precursor B-cell phenotype. CD20 antigen was not expressed on these cells. The data suggest that cytoplasmic mu may be expressed earlier than CD20 antigen in the differentiation of B-cell lineage. The morphologic, cytochemical, and immunophenotypic characteristics did not distinguish these nonneoplastic cells distinctly from leukemic lymphoblastic cells. The increase of small blastoid cells was a transient and self-limited phenomenon, in contrast to that of neoplastic blasts. These cells should be recognized as a common component of the bone marrow of marrow transplant recipients. The significance and role of these cells in immune recovery and hematopoiesis remain uncertain.
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PMID:The transient appearance of small blastoid cells in the marrow after bone marrow transplantation. 161 19

Patients in first remission of acute lymphoblastic leukaemia (ALL) considered to be at high risk of relapse were offered autologous bone marrow transplantation (ABMT) using purged marrow as a therapeutic alternative to cranial irradiation and maintenance chemotherapy. Twenty-seven bone marrows taken in remission, were purged using monoclonal antibodies (anti CD7 for T lineage and anti CD10 and/or anti CD19 for B lineage leukaemias) plus rabbit complement. Retrospective analysis of 19 purged marrows by immunophenotyping or immunoglobulin gene rearrangement studies demonstrated no evidence of disease. Engraftment was seen in 26 of the patients. No correlation was found between the numbers of infused nucleated cells or colony forming units-granulocyte-macrophage (CFU-GM) and subsequent engraftment kinetics. The actuarial disease-free survival (DFS) is 32% at 7 years (median follow-up 3.4 years). There were two transplant related deaths (actuarial risk 8%); the main cause of treatment failure has been disease recurrence with an overall actuarial risk of 67%; 76% for T-ALL (five of nine), 62% for common ALL (five of 10), two of five pre B and none of three patients with B-ALL. In these 27 high risk patients in vitro purging of remission marrow as part of ABMT appears not to improve patient outcome, although confirmation of this would require a randomized trial.
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PMID:Failure of purged autologous bone marrow transplantation in high risk acute lymphoblastic leukaemia in first complete remission. 171 92

A 21-year-old male presented with a large mediastinal mass and a white cell count of 420 x 10(9)/L. A diagnosis of acute lymphoblastic leukemia (ALL) was made, with 90% of cells in the bone marrow (BM) and 99% in the peripheral blood (PB) being lymphoblasts (FAB L1). Cytogenetic analysis of these cells revealed a rare variant of the t(4;11) translocation involving chromosome arm 11p rather than 11q, namely t(4;11)(q21;p14-15). The standard form of the (4;11) translocation has been associated with leukemias with mixed-lineage phenotypes. Three cases of ALL with t(4q;11p) have previously been reported. One of these cases showed phenotypic heterogeneity involving myeloid and lymphoid lineages. The leukemia reported here also exhibits lymphoid/myeloid features. Immunophenotyping of the blasts showed that most of the cells were positive for CD2, CD5, CD7, CD10 (CALLA), CD34, and HLA-DR. A significant proportion of the cells expressed CD33. These results suggest a biphenotypic rather than a biclonal disease. Molecular analysis showed rearrangement of both immunoglobulin heavy-chain genes (JH) and of a single allele of the T-cell receptor (TCR) gamma 1 gene, while retaining germline TCR beta genes.
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PMID:A rare translocation (4;11)(q21;p14-15) in an acute lymphoblastic leukemia expressing T-cell and myeloid markers. 175 71

From 583 cases of acute lymphoblastic leukemia (ALL) and 181 cases of acute myeloid leukemia (AML) in childhood, seven patients were identified to have t(11;19) (q23;p13) by sequential cytogenetic analyses. The t(11;19) was associated with B-precursor ALL at diagnosis in three patients and at relapse in one patient. All four tested patients with B-precursor failed to express the CD10 antigen when the t(11;19) was detected, and one of three patients tested expressed myeloid-associated markers. In three other patients the translocation was detected either at lineage conversion from ALL to M5 AML (n = 2) or from AML to CD10- B-precursor ALL (n = 1). Leukemic blasts of four patients had an entirely different karyotype at the time of lineage conversion or loss of CD10 expression, suggesting an induction of a second neoplasm. Thus the t(11;19) can be found in de novo or secondary acute leukemia with lymphoid (CD10-) or myeloid (monoblastic) phenotype. Further investigation of the gene(s) involved in the 11q23 chromosomal region and the breakpoints in the 19p13 region is needed to understand the leukemogenesis of this apparently heterogeneous group of disorders.
Leukemia 1991 Dec
PMID:Childhood acute leukemia with t(11;19) (q23;p13). 177 55


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