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

We have generated and characterized a highly oncolytic adherent lymphocyte subset (A-LAK) from eight leukemic patients with non-lymphocytic leukemia (NLL) in remission and one NLL patient in relapse. Our studies demonstrated that A-LAK was superior in its oncolytic activity (tested in a 3-h 51Cr release assay) to conventionally prepared (LAK) and non-adherent (NA) IL-2 cultures. No activity was observed by this highly oncolytic subset against normal bone marrow (BM). A-LAK also displayed highest proliferative activity in 7-11 day cultures (5- to 58-fold expansion) in comparison to LAK (0.7- to 2.7-fold) or NA (1.0- to 2.6-fold) cultures. Analysis of phenotype of unseparated, NA and adherent (A-LAK) lymphocytes 24 h after IL-2 activation showed that the A-LAK was composed predominantly of high intensity (bright) CD11a+ (LFA-1) lymphocytes (75 +/- 4.8%) when compared to the other two populations (12 +/- 2.1%). Similarly, A-LAK contained higher proportion of CD11b (CR3 receptor)-positive lymphocytes (39 +/- 2.1%) than unseparated and NA lymphocytes (11 +/- 1.4%). Double marker phenotypic studies showed that A-LAK cultures were heterogeneous and distribution of individual lymphocyte subsets differed among NLL patients. While in A-LAK culture of some patients the CD56+, CD3- natural killer (NK) cell subset was predominant, CD3+, CD56- lymphocyte subset was prevalent in others. Highest A-LAK lytic activity was always correlated with highest NK cell content. Characterization studies (using the complement-depletion technique) showed that independently of the distribution of lymphocytes in A-LAK cultures, CD16+, CD56+, CD3- NK cell subset displayed highest oncolytic effect. CD5+ subset also participated in cytotoxic function. These observations indicated that A-LAK may represent a new therapeutic approach to treatment of leukemia.
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PMID:Highly oncolytic adherent lymphocytes: therapeutic relevance for leukemia. 203 Jun 6

Clinical and biological features were assessed in 114 consecutive previously untreated adult acute myeloid leukaemia (AML) patients whose diagnosis was based on FAB criteria and detailed immunophenotyping. All patients received standard intensive chemotherapy. The main purpose of this study was to establish the prognostic value, if any, of terminal transferase (TdT) expression in myeloid leukaemia. TdT positive cells (7-80% of total blast cells) were detected in 40% of the cases. Among clinical characteristics, a low lactate dehydrogenase (LDH) (less than 250 I.U.) (P = 0.003), a low initial white blood cell count (less than 10 x 10(9)/l) (P = 0.002), and an absolute neutrophil count (less than 5 x 10(9)/l) (P = 0.02) were associated with TdT-positivity. FAB classification was not predictive of TdT expression, and there was no difference in the distribution of FAB subtypes between the groups. Multivariate analysis combining clinical and laboratory data indicated that a low expression of the monocytic antigen CD14 was predictive of TdT positivity in AML (P = 0.01). Karyotyping showed no difference in the pattern of occurrence of specific abnormalities between the TdT+ and the TdT- group. When clinical and immunophenotype data were included in a prognostic model, the patient's age was highly predictive of response (P less than 0.001), and only the CDw65 antigen contributed to the response model (P = 0.07). TdT+ patients with a low expression of CD11b achieved a higher frequency of response at a borderline level of significance (P = 0.06). Frequency of response to chemotherapy, the response duration or overall survival were not influenced by TdT expression.
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PMID:Terminal transferase expression in acute myeloid leukaemia: biology and prognosis. 204 81

The role of interleukin-1 (IL-1) was studied in the proliferation of promyelocytic HL-60 leukemia cells. When HL-60 cells were cultured in 10% fetal calf serum (FCS) containing medium IL-1 did not have any effect on the proliferation. In 1% FCS containing medium, the proliferation of HL-60 cells gradually decreased, but IL-1 was found to be clearly mitogenic for these cells. IL-1 did not function as an autocrine growth factor for HL-60 cells, since anti-IL-1 antibodies did not suppress the basal proliferation of these cells. IL-1 was also mitogenic for U937 but not for THP-1 cells. The suppression of HL-60 proliferation was found to be accompanied with monocytic differentiation as assessed by an increase in HLA-DR, CD11b and CD14 antigen expression. IL-1 could suppress this differentiation. HL-60 cells cultured in 1% FCS were found to express increased amounts of IL-1 receptors on the cell surface.
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PMID:Growth inhibition caused by serum depletion induces differentiation, interleukin 1 receptor expression and interleukin 1 responsiveness in the HL-60 promyelocytic leukemia cell line. 214 Jun 79

A permanent cell line, LEF1, has been established from the cells of an adult suffering from a Philadelphia positive acute lymphoblastic leukemia. The LEF1 cell line was obtained by maintaining peripheral blood cells from the patient in culture on a fibroblast feeder; subsequently, an autonomously growing cell population, independent of that feeder layer, developed. The karyotype of the cell line, 46, t(9;22)(q34;q11), was different from the karyotype at diagnosis which had 53 chromosomes and two Philadelphia chromosomes. Furthermore, compared with the initial leukemic blasts, the immortalized cell had three differences in surface phenotype (CD23+, CD11b-, CD10-). However, molecular studies indicated that the breakpoint in the 3' part of the first intron of the BCR gene was unchanged, confirming the leukemic origin of LEF1. The cell line was shown to be Epstein-Barr virus negative.
Leukemia 1990 May
PMID:A new Ph1+, bcr cell line derived from a patient with ALL-L1 gained autonomy in culture concomitant to CD23 expression. 214 94

We have studied tumor necrosis factor alpha (TNF-alpha) for its capacity to induce differentiation and to modulate c-myc and c-fms protooncogene mRNA expression in fresh blasts from 10 patients with acute myeloblastic leukemia (AML). Bone marrow blast cells were grown in suspension cultures in the presence of 500 U/ml (62 ng/ml) of TNF-alpha for 7 days. Induction of differentiation was assessed by means of morphology, cytochemistry, immunophenotyping (CD11b, CD13, CD14, CD33), and nitroblue tetrazolium reduction. In all cases, exposure of leukemic blasts to TNF-alpha resulted in phenotypic changes consistent with induction of differentiation, although a marked variability in degree and type of response was observed. The majority of cases developed monocytic morphology and showed significant increases (chi 2 test, p less than 0.05) in phagocytic activity and/or expression of ANAE and myelomonocytic differentiation antigens (CD11b, CD14). TNF-alpha reduced c-myc mRNA level over a period of 24 hr in four of six cases studied: the two cases with no down-regulation were the least responsive in terms of myelomonocytic differentiation. These results confirm those obtained with leukemic cell lines, suggesting that TNF-alpha can induce differentiation of fresh AML blasts, mainly toward the monocytic lineage, and that induction of differentiation seems to be closely linked to down-regulation of c-myc mRNA expression over the first 24 hr rather than to attenuation of cellular proliferation per se.
Leukemia 1990 Jun
PMID:Tumor necrosis factor alpha down-regulates c-myc mRNA expression and induces in vitro monocytic differentiation in fresh blast cells from patients with acute myeloblastic leukemia. 235 42

Neutrophil maturation was studied in normal human bone marrow aspirates using multidimensional flow cytometry in comparison with morphology. The combination of the monoclonal antibodies, CD11b, CD15, and CD16, in addition to the forward and orthogonal light scattering signals permitted the isolation of neutrophilic cells from cells of other cell lineages with a purity of greater than 99%. An unexpectedly close relationship was found between the identification of neutrophil maturation by flow cytometry and morphological classification of cells sorted based on cell surface antigen expression and light scattering properties. The neutrophils could be divided into six distinct maturational stages, i.e., stage N I contained predominantly myeloblasts; stage N II, predominantly promyelocytes; stage N III, predominantly early myelocytes; stage N IV, predominantly myelocytes and metamyelocytes; stage N V, predominantly metamyelocytes and bands; and stage VI, predominantly segmented neutrophils. These data suggest that the morphologic changes during neutrophil maturation can be identified by flow cytometry using simultaneous quantitative assessment of multiple antigens in concordance with the light scattering properties of the human bone marrow cells.
Leukemia 1990 Sep
PMID:Flow cytometric analysis of human bone marrow. III. Neutrophil maturation. 239 85

The administration of hydroxyurea (3 x 10(-4) M) and cytosine arabinoside (10(-7) M) greatly induces the expression of the vimentin gene in human promonocytic leukemia U-937 cells. The induction takes place at both the mRNA and protein levels, as demonstrated by Northern blot, immunoblot and immunofluorescence assays. On the contrary, the drugs inhibit the expression of c-myc and ornithine decarboxylase, and do not modify significantly the expression of beta-actin. Since hydroxyurea and cytosine arabinoside trigger the phenotypic differentiation of U-937 cells, as demonstrated by the induction of the differentiation-specific CD11b and CD11c antigens, it is concluded that vimentin expression might be implicated in the maturation of these cells.
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PMID:S-phase inhibitors induce vimentin expression in human promonocytic U-937 cells. 259 4

Murine monoclonal antibodies to human myeloid cell surface differentiation antigens were prepared using the myelomonocytic leukemia cell line RC-2A as immunogen. Using a highly sensitive colorimetric assay, antibodies were selected as myeloid-associated based on their binding to RC-2A cells, but not to cells of the autologous EBV-transformed* B cell line Cess-B. Antibodies to five distinct cell surface antigens were extensively characterized for their binding to normal and leukemic hemopoietic cells, and to tissue sections. Three antibodies may identify antigens previously described in the International Leucocyte Typing Workshops (CD14, CD11b and CD31). The other two antigens appear to be expressed at low levels on the surface of RC-2A cells, and do not correspond to existing CD groups. One of these is also present on monocytes and neutrophils. Both were present on myeloid progenitor cells, as judged by depletion experiments with antibody and complement, although neither bound appreciably to myeloid leukemic cells as judged by indirect immunofluorescence. The other three antibodies bound preferentially to leukemic specimens displaying monocytic differentiation. Four of the antibodies could be demonstrated to bind to cells in frozen sections of tonsil and small intestine and all gave distinct patterns of reactivity. In particular, these antibodies differed markedly in their binding to endothelium, follicular dendritic cells and various types of tissue macrophages. These antibodies may be useful in the study of the differentiation of myeloid cells and in studies of immunologically mediated disease such as allograft rejection.
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PMID:Human myeloid differentiation antigens identified by monoclonal antibodies to the myelomonocytic leukemia cell line RC-2A. 314 80

Blast cells from eight patients with erythroleukaemia and one with erythroid blast crisis of chronic myeloid leukaemia were studied for the co-expression of cell surface myeloid and erythroid markers, and the phenotype compared with that of erythroblasts from two patients with megaloblastic anaemia. The technique of dual indirect immunofluorescence was used with a panel of seven mouse monoclonal antibodies against well-defined myeloid antigens (CD11b, 13, 14, 15, 33 and HLA-DR) and a rat antibody, YTH89.1, specific for glycophorin A. No dual fluorescence, emanating from myeloid or erythroid lineage markers, was found to occur in either the neoplastic or non-neoplastic erythroid cells studied. These data support the hypothesis that lineage fidelity is conserved in leukaemia.
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PMID:Erythromyeloid lineage fidelity is conserved in erythroleukaemia. 318 81

We studied the clinical and biologic features of 10 cases of acute leukemia that met standard French-American-British (FAB) criteria for acute myeloid leukemia (AML) but in which the blast cells also expressed the T-cell-associated CD2 surface antigen. All cases had greater than 3% myeloperoxidase and Sudan black B-positive leukemic blasts, and blasts from seven cases contained Auer rods. Reactivity of the cells with a panel of monoclonal antibodies (MAbs) indicated that leukemic cells in all cases expressed myeloid-associated (CD11b, CD13) surface antigens, further supporting the diagnosis of AML. However, blasts from every patient coexpressed the T-cell-associated surface CD2 and CD7 as well as cytoplasmic CD3 antigens. Blasts from five patients expressed surface CD25, whereas blasts from only one expressed surface CD3. Five patients had rearranged T-cell receptor beta-chain genes, whereas only three had rearranged T-cell receptor gamma-chain genes. This pattern of lineage-related gene expression appears to define a distinct subtype of AML with T-lymphoid features (CD2+ AML) and could reflect either aberrant gene expression in leukemic blasts or transformation of a pluripotent stem cell having a flexible pattern of gene expression. Clinically, these 10 patients presented at an older age with a higher leukocyte count and a higher frequency of lymphadenopathy than did children whose blast cells were characteristic of myeloid leukemia. Patients with CD2+ AML also had poorer responses to remission induction therapy (50% v 80% entered complete remission, P = .05). However, each of the five children who failed induction chemotherapy on AML protocols had a striking response to drug combinations usually reserved for lymphoid leukemia. We conclude that this leukemia with mixed lymphoid and myeloid characteristics is a distinct biologic and clinical entity.
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PMID:Acute myeloid leukemia with T-lymphoid features: a distinct biologic and clinical entity. 326 Nov 83


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