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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe in vitro studies undertaken to characterize the expression of the proto-oncogene c-jun during differentiation of B-CLL cells. The phorbol ester TPA and the natural compound Bryostatin 1 (Bryo) were used to directly stimulate protein kinase C (PKC) while the calcium ionophone A23187 was employed to increase intracellular Ca2+. In quiescent cells c-jun mRNA expression was undetectable or at low levels. Upon treatment with TPA or Bryo, the steady-state levels of c-jun mRNA increased rapidly, reached a maximum at 0.5 or 1 hr, and then decreased in the B-CLL cells from all five patients analyzed; this reaction was augmented by the addition of A23187. Induction of c-jun mRNA by direct stimulation of PKC could be blocked by the PKC inhibitor H7. The present observations, along with other results on the induction of long-term phenotypical cellular changes, such as alteration of morphology and other features of differentiation, support the notion that the second messenger (via PKC) and the third messenger (via proto-oncogene products) pathways are intact in B-chronic lymphocytic leukemia cells.
Leukemia 1990 Jun
PMID:Expression of proto-oncogene c-jun during differentiation of B-chronic lymphocytic leukemia. 211 1

T and NK cell blood subpopulations were determined in 33 patients with B-CLL and in 14 patients with B-MLUS by two-color immunofluorescence. CLL patients had significantly higher total numbers of Leu-7+ and CD8+ cells and lower numbers of CD16+/Leu-7- cells as well as a higher Leu-7/CD16 ratio and a lower CD4/CD8 ratio than MLUS patients and control donors. Moreover, MLUS patients exhibited a significantly lower Leu-7/CD16 ratio as well as a higher frequency of CD16+/Leu-7- cells than healthy donors. These results suggest that B-CLL patients have higher numbers of circulating immature NK cells compared to B-MLUS, while B-MLUS patients have a larger proportion of NK cells with a high lytic capability as compared to both CLL and normal controls. The imbalance between CD4+ and CD8+ cells was prominent in CLL with a low CD4/CD8 ratio, but within the upper normal range in MLUS. Differences in immunoregulatory cell subpopulations between B-CLL and B-MLUS might therefore contribute to the different clinical behavior of these two disorders.
Leukemia 1989 Jul
PMID:Differences in blood T and NK cell populations between chronic lymphocytic leukemia of B cell type (B-CLL) and monoclonal B-lymphocytosis of undetermined significance (B-MLUS). 247 2

Normal B lymphocytes are characterized by rearrangement and expression of immunoglobulin genes, but not of T cell receptor genes. These properties might assist in lineage assignment, but there are examples of fresh leukemic cells and of cell lines where exceptions to this rule have been noted. We have studied cell samples of patients with B-CLL for expression of TCR alpha and beta chain genes. Using in situ hybridization with fluorescein-labeled probes, TCR alpha mRNA was found to be expressed in 14 of 18 samples and TCR beta mRNA in 7 of 16 samples. Specificity of hybridization was demonstrated by near complete blockade of TCR alpha hybridization with unlabeled TCR alpha, but not with unlabeled TCR beta probe. Furthermore, in Northern blot analysis a truncated 1,4 kb message for TCR alpha was readily detectable. No significant cell surface staining with the anti-TCR alpha/beta monoclonal antibody WT31 was observed. A contribution of T cells within the leukemic sample could be excluded since only samples with leukemic cell counts of greater than 50,000 cells/mm3 and only samples with 5% or less CD2+ T lymphocytes were studied. Our data show that a large proportion of B-CLL samples may express a truncated version of the TCR alpha message, indicating that this gene can be activated in leukemic B cells frozen at a late stage of differentiation.
Leukemia 1989 Jul
PMID:T cell receptor alpha expression in B-type chronic lymphocytic leukemia. 252 11

Trisomy 12 is the most common chromosomal aberration in chronic B lymphocytic leukemia (B-CLL). In this study we have investigated trisomy 12 and posed two major questions: (a) What is the origin of the third copy of chromosome 12? and (b) What is the proportion of trisomy 12 cells in malignant clones with this aberration? The origin of an extra copy of chromosome 12 in lymphocytes from patients with B-CLL was studied by the use of probes detecting restriction fragment length polymorphisms on this chromosome. In all six patients that were evaluable, the third copy was derived from a simple duplication of one of the original chromosomes. In none of these patients nor in four patients with two copies of chromosome 12 were losses of the homologue observed. When studying metaphase cells from some CLL patients with trisomy 12, a large proportion of the cells are found to have a normal karyotype. In this study the fraction of normal metaphases was not matched by a similar fraction of cells lacking trisomy 12, as judged by scanning densitometry of hybridization bands. Thus, normal metaphases appear to be derived from a small fraction of easily stimulated probably nonmalignant cells and not from a large second population of malignant cells with a normal karyotype.
Leukemia 1989 Dec
PMID:Molecular analyses of chromosome 12 in chronic lymphocytic leukemia. 258 80

Three cellular or putative oncogenes: c-myc, bcl1, and bcl2 were previously found to be rearranged in some B cell malignancies due to chromosomal translocations. Data concerning the role of such genetic rearrangements in B-CLL are very scanty and limited to few cases in which bcl1 rearrangements were found. We studied DNA samples from 38 cases of B-CLL by Southern blot technique in order to find out the existence and frequency of such events. No bcl1 or bcl2 rearrangements were found in any of the studied cases; thus, involvement of these genes in CLL must be rare. In one patient who had an aggressive and resistant disease, c-myc rearrangement was found.
Leukemia 1989 Jan
PMID:A search for bcl1, bcl2, and c-myc oncogene rearrangements in chronic lymphocytic leukemia. 264 78

In this paper we communicate that cells of a selected B-CLL clone (I83), after 2 days of Staphylococcus aureus Cowan strain 1 (SAC) activation, respond to recombinant IL-2 (rIL-2) and a B cell stimulatory factor (BSF-MP6) and act in strong synergism with induction of simultaneous high-rate proliferation and differentiation. None of the factors alone or other lymphokines (IFN-gamma, TNF-alpha, 12 kDa BCGF, IL-1, IL-4, IL-5, IL-6) induced significant DNA synthesis in SAC-activated cells. However, low levels of IgM were produced by cells stimulated by SAC + rIL-2. The SAC activation was followed by an increase in IL-2 receptor (IL-2R; CD25) expression, and the proliferation induced by BSF-MP6 + rIL-2 could be blocked in a dose-dependent manner by alpha-CD25 antibody. Furthermore, flow cytometric cell cycle studies showed that SAC and BSF-MP6 + rIL-2 stimulated cells underwent a complete transition through the cell cycle to become arrested in G1. The induced proliferation by BSF-MP6 + rIL-2 was dependent on serum but independent of the 2.8% of CD4, CD8, CD14, and CD16 positive cells contaminating the I83 cell population. Previously, we reported that I83 cells activated by 12-O-tetradecanoylphorbol-13-acetate (TPA) were induced to differentiation only but that the addition of BSF-MP6 induced DNA synthesis concomitantly with the differentiation. This paper demonstrates that physiological stimuli can induce both high-rate proliferation and differentiation in a B-CLL clone in vitro. It also suggests that the low proliferation and the differentiation block in vivo, characteristic of most B-CLLs, may reflect a subnormal response of B-CLL cells to growth and differentiation factors, or a dysfunction in the factor production by the patients' T cells.
Leukemia 1989 Aug
PMID:Interleukin-2 and a T cell hybridoma (MP6) derived B cell-stimulatory factor act synergistically to induce proliferation and differentiation of human B-chronic lymphocytic leukemia cells. 217 41

Leukemia cells from a patient with chronic lymphocytic leukemia (CLL) were found to bind sheep RBC (SRBC) through their monoclonal surface IgM. A lymphoblastoid cell line was obtained by immortalization of leukemic cells with Epstein-Barr virus (EBV). Cultured leukemic cells were found to have a supernumerary chromosome 12, an abnormality typical of CLL of the B cell type. To our knowledge, this is the first EBV-immortalized cell line from B-CLL cells of known SRBC specificity and the third reported CLL cell line carrying trisomy of chromosome 12.
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PMID:Establishment of a new Epstein-Barr virus-immortalized cell line from chronic lymphocytic leukemia with trisomy of chromosome 12 that produces monoclonal IgM against a sheep RBC antigen. 282 46

The binding of alpha 2-interferon to highly purified plasma membrane proteins of malignant human lymphoid cells was assessed by Western Blotting. The human hairy cell leukemia cell line JOK-1 revealed three major alpha-interferon binding proteins with molecular weights of 120, 100, and 32 kD. Pretreatment of JOK-1 cells with alpha-interferon in vitro results in a disappearance of these proteins, which is in concordance with receptor down-regulation on JOK-1 cells. In a case of T chronic lymphocytic leukemic (CLL), a differential binding pattern of two proteins with 100 and 85 kD was observed, whereas a case of B-CLL did not yield any signal detection. In addition, mononuclear cells from patients with hairy cell leukemia and CLL were found to differ with respect to the in vitro incorporation of nucleic acid precursors. alpha 2-Interferon enhances [3H] uridine incorporation into hairy cells, whereas this phenomenon can be detected in CLL cells only to a much lesser extent.
Leukemia 1987 Apr
PMID:Effect of alpha 2-interferon on hairy cells and cell lines: a role for type I interferon receptors and RNA synthesis. 295 26

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

We have classified 200 cases of lymphoid leukemia and non-Hodgkin lymphoma (LL and L) typed with as many monoclonal antibodies as possible for each case in the WHO Leukemia and Lymphoma categorisation modified according to the today knowledge of normal cell differentiation. We have found that the lymphoid acute leukemias correspond respectively to normal differentiation steps: the [microblastic] to the polyvalent stem cell TdT+, Ia+, B4- or to the lymphoid progenitor TdT+, Ia+, B4-; the [prolymphoblastic T] to the prothymocyte TdT+, OKT11+, OKT10+, 9+, 6-, 4-, 8-; the [prolymphoblastic non T] to the B precursor B4+, B1+, J5+, C mu-, sIg-; the [T-macrolymphoblastic] to the OKT6+ thymocyte; the [B-macrolymphoblastic] to the large pre-B C mu+; the [prolymphocytic T] to the OKT6-, 3+, 4+ and 8+ thymocyte; the [prolymphocytic B] to the small pre-B C mu+; the Burkitt's leukemia to a pre-B cell transformed into a lymphoblastoid cell sIg mu. The B-CLL is constituted of sIg mu+, gamma-, Ia+, B4+, B1+, FC+ virgin lymphocytes and the T-cell either of OKT3+, 4+ or of 8+ peripheral T-lymphocyte, the mantle zone B- lymphoma is constituted of sIg mu+, FC- primary lymphocytes. The B-centro-follicular lymphomas are made of sIg mu+, delta+, gamma+ either small cell cleaved, or large cell. The Burkitt's and non-endemic Burkitt's lymphomas are made of transformed cells into sIg mu+ lymphoblastoid B-cells. We have described a non-blastic, non-Burkitt's, non-follicular, medium cell lymphoma sIg+. The B-immunoblastic lymphoma is sIg mu+, delta-, gamma+, FC+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lymphoid leukemia and non-Hodgkin's lymphoma type continuum, superimposed to lymphocyte differentiation step continuum. A proposition for a revised W. H. O. lympiioid leukemia-lymphoma categorisation. 386 94


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