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

Leukaemic cells from 2 patients with B-prolymphocytic leukaemia were immortalized in vitro by means of Epstein-Barr virus and phorbol-ester TPA. The resulting cell lines, named JVM-2 and JVM-3, have been growing continuously in liquid culture for more than one year. JVM-2 is characterized cytogenetically by t(11;14)(q13; q32), and JVM-3 by trisomy 12. The immunoglobulin (Ig) heavy- and light-chain genes showed the same pattern of rearrangement in both lines as in the original prolymphocytes from each case. The cells from these lines showed a spectrum of morphological and immunological features corresponding to different stages of B-cell maturation. The expression of Ig, IgM-lambda in JVM-2 and IgMD-K in JVM-3, changed from a predominantly membrane pattern in the original cells to a cytoplasmic one in the cell lines. By comparison with their original progenitors, the cells from both lines showed reduced reactivity with the monoclonal antibody (MAb) FMC7, and increased expression of the antigens recognized by the MAbs OKT10, alpha-Tac, FMC53 and Ki-I. The availability of cell lines from this rare type of lymphoid leukaemia offers a potential tool for the study of molecular events associated with the expression of Ig and other antigens by neoplastic cells.
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PMID:Two new cell lines from B-prolymphocytic leukaemia: characterization by morphology, immunological markers, karyotype and Ig gene rearrangement. 309 93

The regulation of IgM synthesis and secretion was studied in chronic lymphocytic leukemia cells, with a phenotype roughly similar to peripheral resting B cells, during phorbol ester (12-O-tetradecanoylphorbol-13-acetate)-induced differentiation. TPA treatment caused a 20 times increase in total RNA synthesis and 20 to 50 times increase in the protein synthesis as compared to control cells. Morphologically, 70-90% of the cells reached the lympho- or plasmablast stage of differentiation. In control culture cells, approximately equal amounts of mRNA coding for secretory (s) and membrane (m) mu-chains were found. The micron message was translated as surface IgM expression was detected. A posttranscriptional regulation of microsecond synthesis appears to exist, since only low amounts of cytoplasmic mu-chains were detected by immunoprecipitation and SDS-PAGE, and no secretion of pentameric IgM was detected as measured by an RIA. TPA induction caused a relative increase in the microseconds to microns mRNA ratio, demonstrating differentiation associated control mechanisms operating at the level of mRNA processing. The high levels of cytoplasmic microsecond-chain precursor and the efficient secretion of pentameric IgM in TPA-induced chronic lymphocytic leukemia cells indicated the presence also of posttranscriptional controls.
Leukemia 1987 Jan
PMID:TPA-induced differentiation of chronic lymphocytic leukemia cells: studies on mu-chain expression. 311 1

We have studied the expression and function of interleukin-2 (IL-2) receptors on B cell precursor acute lymphoblastic leukemias (ALL). After incubation of B cell precursor ALL in vitro for 24 hr, 11 out of 17 leukemic bone marrow aspirates expressed the Tac/CD25 protein (greater than 10% positive blasts). Expression of Tac/CD25 on the leukemic cells was confirmed by two color flow cytometric analysis using anti-Tac/CD25 and anti-CALLA/CD10 monoclonal antibodies. The molecular mass of the B cell precursor ALL Tac/CD25 protein was 55 kilodaltons (kD), identical to that on activated T cells. Binding of radiolabeled IL-2 in two leukemic bone marrow aspirates demonstrated the presence of high affinity IL-2 receptors. Cross-linking of 125I-labeled IL-2 to TPA activated B cell precursor ALL revealed the 55 kD Tac/CD25 protein and an additional protein of 75 kD. Recombinant IL-2 in concentrations of 10-1,000 U/ml had essentially no proliferative effect in 10 patients tested, whereas low molecular weight B cell growth factor (L-BCGF) induced proliferation in 8 of 10 patients. L-BCGF also induced expression of CD20 in 3 of 7 CD20 negative B cell precursor ALL. IL-2 did not induce CD20, but enhanced its expression in the 3 patients who responded to L-BCGF. We conclude that IL-2 has essentially no proliferative effect on B cell precursor ALL, despite the presence of high affinity IL-2 receptors and the presence of the IL-2 binding cell surface molecules similar to those on activated T cells. IL-2 may, however, induce a phenotypic change (CD20 acquisition) consonant with differentiation in synergy with L-BCGF.
Leukemia 1987 Sep
PMID:Structure/function analyses of IL-2 binding proteins on human B cell precursor acute lymphoblastic leukemias. 311 14

Chronic B-lymphocytic leukemia (B-CLL) cells from 10 patients were cultured serum-free with recombinant interferon (rIFN)-alpha 2, rIFN-gamma, or phorbol ester (TPA) for 5 days. All three agents induced functional differentiation, as evidenced by IgM secretion, without concomitant proliferation. A panel of monoclonal antibodies was used to detect changes in cell surface antigens defining pre-B cells (CALLA), resting B cells (HH1), early (4F2, MHM6) and late (anti-Tac, OKT9) B cell activation, and terminally differentiated B cells (OKT10). The activation markers 4F2, MHM6, and anti-Tac and the plasma cell marker T10 were all significantly induced with TPA, rIFN-alpha 2, an rIFN-gamma, whereas the expression of HH1 decreased. CALLA was detected on substantial proportions of differentiated (4-38%) but not resting (0-4%) B-CLL cells. The CALLA-positive B-CLL cells were negative for nuclear terminal deoxynucleotidyl transferase (TdT). The T9 antigen was expressed on TPA-treated cells (1-16%) only. The present findings indicate novel properties of IFN-alpha and IFN-gamma in inducing terminal differentiation of human monoclonal B cells without prior activation.
Leukemia 1987 Sep
PMID:Effects of recombinant interferon-alpha and -gamma on B-CLL cells in serum-free medium: expression of activation, differentiation, and CALLA antigens. 311 15

Protein phosphorylation mediated by murine IL3 and other factors has been studied in two different IL3-dependent lines, AC2 and 123. In both lines, responses to rat recombinant IL3 are enhanced or induced by growth in rat spleen lymphocyte conditioned medium. Growth stimulation by murine and rat IL3, by rat lymphokine(s), and by ATP in ATP-responsive cells is closely associated with the rapid (2-4 min) phosphorylation of a 33-kDa protein (p33) in all the cells examined. p33 phosphorylation is not stimulated by another lymphokine, IL4, nor by TPA or calcium ionophore alone, which are unable to stimulate growth by themselves, and is independent of serum. p33 phosphorylation is inhibited by trifluoperazine, an inhibitor of calcium-calmodulin, but is less sensitive to inhibition by H7, an inhibitor of protein kinase c, in AC2 cells. A spontaneous IL3-independent clone of AC2 (AC-) has been isolated. AC- cells are aggressively leukemic, do not produce detectable IL3, but phosphorylate p33 constitutively where it is associated with a particulate cell fraction. It is suggested that p33 is a common intermediate molecule involved in signal transduction by the various ligands which result in growth stimulation and that its constitutive phosphorylation may play a key role in the maintenance of the leukemic state.
Leukemia 1988 Feb
PMID:Rapid phosphorylation of a specific 33-kDa protein (p33) associated with growth stimulated by murine and rat IL3 in different IL3-dependent cell lines, and its constitutive expression in a malignant independent clone. 312 92

Monoclonal populations from 10 cases of phenotypically well-characterized B-chronic lymphocytic leukemia (B-CLL) and from a single case of hairy cell leukemia were assessed for their ability to respond by mitogenic stimulation to a number of agents described as growth-promoting for normal B cells. These included the recombinant factors interleukin-1 (IL1), IL2, IL4, IL5, and gamma-interferon, partially purified B cell growth factor (BCGF), B cell stimulatory factor 2 (BSF2), and a CDw40 antibody to the Bp50 antigen. With only few exceptions, no factor or combination of factors stimulated B-CLL populations directly to DNA synthesis. By marked contrast, the hairy cells were responsive to IL4, BCGF, and the CDw40 antibody. B-CLL cells could become responsive with the inclusion of the phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) as co-stimulant such that half of the populations were now activated by IL4, particularly when BCGF was also present. Populations refractory to IL4 were, nonetheless, still responsive to BCGF. In only three cases was a significant effect seen with IL2. gamma-interferon could be either inhibitory or stimulatory and, in a few cases, modulated specifically the effects of IL4. In contrast to normal B cell activations, neither the CDw40 antibody nor a calcium ionophore synergized with TPA for stimulating the majority of B-CLL populations. BSF2 was stimulatory in the two cases examined while both IL1 and IL5 were ineffective where studied. No simple correlation was observed between the patterns of responsiveness and the expression of a panel of CD markers assayed on cells both freshly isolated and after TPA stimulation. The data demonstrate a functional heterogeneity not disclosed by simple phenotypic analysis and also indicate the range of activities which can impinge on the growth regulation of monoclonal B cell populations.
Leukemia 1988 Mar
PMID:Stimulation of B-chronic lymphocytic leukemia populations by recombinant interleukin-4 and other defined growth-promoting agents. 312 69

We report here experiments on the analysis of cellular signal transduction in a series of patients with chronic B cell disorders (B cell chronic lymphocytic leukemia [B-CLL] and prolymphocytic leukemia). We compared the response of the leukemic cells with primary external signals (interleukin 2 [IL-2] or B cell differentiation factors [BCDF or IL-6]) with their response to secondary inducers (the phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA] or the calcium ionophore A23187) that circumvent the first part of the signal transduction pathway by directly activating the key enzyme protein kinase C. One BCDF was synthesized by mitogen-activated peripheral blood B lymphocytes; a second BCDF was constitutively produced by the human bladder carcinoma cell line T24. Changes in morphology, Tac (IL-2 receptor) expression, RNA synthesis measured by 3H-uridine uptake, and immunoglobulin production tested by enzyme-linked immunosorbent assay were used as parameters of successful signal transduction. TPA alone and TPA plus A23187 (synergistically) effectively initiated differentiation in all the leukemia cases. Neither IL-2 nor BCDF (singly or in combinations) caused equivalent responses. On the other hand, IL-2 and BCDF produced a substantial differentiation effect on normal B lymphocytes. Our data suggest that (a) B-CLL cells are able to respond to direct stimulation of the second messenger pathway (through protein kinase C) but not to the physiological stimuli IL-2 or BCDF; (b) the defect in signal transduction appears to be located upstream of protein kinase C (a possible candidate is a G protein); (c) malignant B cells may spontaneously or after treatment with inducers express the IL-2 receptor (Tac antigen) in the absence of a functional differentiating response to IL-2; and (d) signs of proliferation/differentiation in B-CLL samples after incubation with IL-2 or BCDF might be due to contamination of the cell populations with residual normal B cells.
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PMID:Analysis of signal transduction in B chronic lymphocytic leukemia cells. 312 49

The effects of exogenously added glycosphingolipids on the differentiation of mouse myeloid leukemia cells (M1-T22) have been studied. Eight gangliosides and ten neutral glycosphingolipids were tested in terms of their induction of phagocytic activities on the leukemia cells. N-Acetyl-neuraminosyllactosylceramide (NAc-GM3) was the most effective glycolipid for inducing the activity. By the addition of 25 micrograms/ml of NAc-GM3, about 70 percent of the cells acquired phagocytic activity within 20 h incubation. GM1a showed about half the activity of the GM3. In the case of the neutral glycosphingolipids, lactosylceramide (CDH) and globotriaosylceramide (CTH) showed significant effects on the induction of phagocytic activity. Preincubation of the cells with the NAc-GM3 enhanced the effect of dexamethasone as a differentiation inducer on M1-T22 cells. When a human promyelocytic leukemia cell line, HL-60, was preincubated with the NAc-GM3 ganglioside, induction of the phagocytic activity, together with inhibition of the cell growth by phorbol ester (TPA), were markedly enhanced. From these observations, the NAc-GM3 ganglioside seems to act as a modulator of differentiation of mouse myeloid leukemia cells and also of HL-60 cells.
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PMID:Ganglioside GM3 as a modulator of differentiation of mouse myeloid leukemia cells (M1-T22). 316 59

PBMC concentrated from 12 patients with CLL were incubated for up to 6 days with various doses of TPA or RA in an attempt to induce differentiation. The results show a great heterogeneity in the cellular response to both inducers. TPA produced two major changes in B-CLL cells, namely the development of some hairy-cell leukemia features with an increase in Ig secretion and the expression of Leu M5 and TAC receptors. In contrast to TPA, RA induced only modest or no changes in surface, but increased numbers of large macrophages were seen as assessed by latex-bead ingestion, expression of Fc receptors and cytochemistry. These changes were more obvious after exposure to RA than to TPA. Thus, while TPA induces mostly differentiation and hairy-cell features in B-lymphocytes, RA induces activation of the monocyte pool with no obvious changes in the lymphocytic compartment.
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PMID:Effects of retinoic acid and phorbol ester on lymphocytes and monocytes in B-lymphocytic leukemia. 320 6

After four days of treatment with 10(-8) M TPA, differentiation of the human T-lymphoblastoid cell line MOLT-4 was induced along the T cell lineage, confirmed by a fall in adenosine deaminase and 5'-ectonucleotidase and a rise in purine nucleoside phosphorylase activity. TPA-treated cells became resistant to the cytotoxic effects of 1-beta-D-arabinofuranosylcytosine (Ara-C), 9-beta-D-arabinofuranosyladenine (Ara-A), and 2-chlorodeoxyadenosine. This was, in part, due to the altered cell cycle distribution (accumulation of cells in the G1 phase), since the toxicity of Ara-C and Ara-A is S phase specific. The diminished rate of Ara-C transport concomitant with Ara-CTP formation after TPA treatment is considered to be the biochemical basis for this acquired resistance.
Leukemia 1988 Jul
PMID:Changes in sensitivity to anticancer drugs during TPA-induced cellular differentiation in a human T-lymphoblastoid cell line (MOLT-4). 326 Jun 48


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