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

A human leukemia cell line, PER-255, was established from the bone marrow of a 5-year-old boy with features typical of lymphomatous T-acute lymphoblastic leukemia (T-ALL). The leukemic origin of cell line PER-255 is indicated by its cytochemical and immunologic similarity to the patient's fresh leukemic cells, which correspond to immature cortical thymocytes. Southern blot analysis showed that the IgJH genes were in germline configuration, whereas both alleles of the T-cell receptor-beta (TCR-beta) gene were rearranged in PER-255 cells, with identical rearrangements present in the patient's leukemic cells. Cytogenetic analysis of the cell line revealed a single abnormal clone with the karyotype 46,XY,t(7;10)(q32-34;q24),t(9;12) (p22;p12-13). Reciprocal translocations involving chromosome bands 7q32-36, containing the gene for the TCR-beta chain, have been reported for a number of tumors of T-cell origin. Translocations involving the 7q32-36 region appear to be nonrandomly associated with childhood T-ALL, whereas abnormalities of 9p and 12p have been reported to be nonrandomly involved in ALL but not specifically associated with the T-cell phenotype.
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PMID:Establishment and characterization of a childhood T-cell acute lymphoblastic leukemia cell line, PER-255, with chromosome abnormalities involving 7q32-34 in association with T-cell receptor-beta gene rearrangement. 254 23

Human chromosomal band 11p13 has been implicated in T cell malignancies carrying t(11;14)(p13;q11) reciprocal translocations and has also been associated with Wilms' tumor and aniridia in a mechanism characterized by overlapping hemizygous constitutional deletions spanning this region. Using probes derived from the T cell receptor delta gene, we have cloned the chromosomal breakpoint in an acute T cell leukemia (T-ALL). Southern blotting analyses of mouse-human somatic cell hybrids from this human T-ALL sample and Chinese hamster-human somatic cell hybrids derived from Wilms' tumor lines have indicated that the 11p13 locus, tcl-2, juxtaposed to the TCR (T cell receptor) delta locus in T cell leukemia, is within the constitutional deletion of two Wilms' tumor-aniridia cases.
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PMID:The chromosome 11 region flanking the t(11;14) breakpoint in human T-ALL is deleted in Wilms' tumor hybrids. 255 34

Radiation leukemia virus (RadLV)-induced thymomas and malignant thymocytes from AKR mice have been shown to bind specifically retrovirus produced by these cell lines. Each lymphoma has been shown to have greatest specificity for cognate virus suggestive of an immune-specific receptor. The question of receptor identity has been addressed here using the RadLV-induced murine T cell lymphoma, C6VL/1, and antibodies specific for known cell surface determinants present on these cells. This lymphoma has been shown to bind both homologous and heterologous RadLV isolates, but to have greatest specificity for homologous retrovirus since homologous free virions can best block the interaction between cells and virus adhered to the wells of a microtitre plate. A clonotypic anti-TCR antibody has been shown to completely inhibit C6VL/1 binding to the homologous virus, RadLV/C6VL, but not to the heterologous virus, RadLV/VL3. Anti-CD4, anti-Thy1.2 as well as anti-H-2Kb and not anti-H-2Db antibodies were found to partially inhibit the interaction with both RadLV/C6VL and RadLV/VL3, yet neither of these virus preparations appears to be contaminated with Class I molecules as measured by radioimmunoassay. The binding interaction between C6VL/1 and RadLV/C6VL appears specifically to involve the TCR since antibody against the clonotypic site on the TCR heterodimer uniquely inhibits this interaction, while the binding of C6VL/1 to RadLV/VL3 appears to involve the H-2Kb molecule. When free virus particles were absorbed to receptors on C6VL/1, both RadLV/VL3 and RadLV/C6VL inhibited the binding of antibody to the TCR and CD4 molecules, while the binding of several anti-H-2Kb antibodies was specifically inhibited by RadLV/VL3. There are at least two known T cell surface structures involved in the interaction of the T cell lymphoma, C6VL/1, with RadLV. These are the TCR complex (comprising the TCR heterodimer and CD4), and the Class I H-2Kb molecule. Since the TCR molecule has been shown to comodulate with H-2Kb molecules when cells were cultured in the presence of anti-H-2Kb antibodies, and the CD4 and H-2Kb molecules have been shown to comodulate with the TCR on only a subpopulation of C6VL/1 cells treated with anti-TCR antibody, this suggests that the H-2Kb molecule may also be part of the larger molecular complex including CD4/8 which can form around the TCR heterodimer.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Binding of radiation leukemia viruses to a thymic lymphoma involves some class I molecules on the T cell as well as the T cell receptor complex. 255 69

To elucidate mechanisms that regulate ordered and tissue-specific assembly of Ig and TCR variable region gene segments, we have introduced a recombination substrate comprised of germline TCR beta V, D, and J gene segments into an Abelson murine leukemia virus-transformed pre-B cell line that actively rearranges endogenous Ig H chain variable region gene segments but does not rearrange endogenous light chain or TCR variable region gene segments. We find that these cells efficiently join D beta segments to J beta segments within the mini-locus, but that they do not make any detectable site-specific rearrangements of the introduced V beta segment even though it is closely linked in the same construct to the D beta. These findings suggest that factors necessary for V beta to (D beta)J beta joining may be absent in these pre-B cells and also imply that the order in which TCR V beta, D beta, and J beta segments are rearranged can be influenced by factors other than the 12/23 recombination rule. Furthermore, in agreement with the an accessibility model of VDJ recombinase control, the D beta region of the construct was found to be relatively more sensitive to DNAase I digestion in isolated nuclei when compared to the unrearranged V beta region.
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PMID:T cell receptor DJ but not VDJ rearrangement within a recombination substrate introduced into a pre-B cell line. 256 55

Clinical and experimental data suggest a role for the immune response in preventing leukemic relapses following allogeneic bone marrow transplantation the graft-versus-leukemia (GVL) effect. In the context of an allogeneic BMT, a number of different immune mechanisms mediated by donor cells may be responsible for the GVL effect. We have approached this question by using limiting dilution cultures of alloactivated human lymphocytes to analyze the in vitro allogeneic cytolytic response against fresh allogeneic leukemia. Initial results in the limiting dilution assays with split culture analyses demonstrated frequent alloreactive cytolytic T lymphocyte precursors that destroyed remission peripheral blood lymphocytes and leukemic cells from the allogeneic leukemic patient. These assays also demonstrated frequent lymphokine-activated killer (LAK) cell precursors that lysed both the LAK sensitive Daudi line and the allogeneic leukemia. In these experiments, isolated cultures also showed cytolytic activity directed against the allogeneic leukemic blasts without activity against remission PBL, or the LAK-sensitive Daudi cell line. Two T cell lines (ABL1 and ABL2) isolated from an LDA, demonstrated this form of specificity, mediating destruction specifically against the allogeneic acute lymphoblastic leukemic cells. Both cell lines ABL1 and ABL2 were CD3+, TCR alpha beta +, and CD4+. These 2 cell lines mediated little or no cytotoxicity against a large panel of other targets tested (natural killer sensitive and resistant cell lines, allogeneic PBL, and allogeneic fresh leukemic blasts). Antibody-blocking experiments revealed a role for the CD3-TCR receptor of both cell lines in lysis of leukemic cells; the CD4 and MHC class II molecules were clearly involved in the lysis by the ABL1 cell line. Specificity of recognition for the allogeneic leukemic blasts was further confirmed by unlabeled target competitive inhibition studies. The mechanism of the preferential lysis of leukemia by the alloactivated T cell lines described in this paper remains uncertain. Nevertheless, these leukemic-specific populations provide a means by which the human GVL effect may be further studied in vitro.
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PMID:Specific recognition of human leukemic cells by allogeneic T cell lines. 257 Dec 6

Human T-cell leukemia virus type I (HTLV-I) is etiologically associated with adult T-cell leukemia, an aggressive lymphoproliferative disorder, and with chronic neurological diseases. In vitro it can infect several types of cells but transforms only human T lymphocytes. We have previously shown that HTLV-I viral particles, even when noninfectious, were able to activate human resting T lymphocytes, suggesting that this activation step may be important in the initiation of the lymphoproliferative process. In the present study, we first demonstrate that in contrast to other mitogenic stimuli, HTLV-I has the unique property to activate human resting T cells in the absence of accessory cells. We then investigate the relationship between HTLV-I-induced T-cell activation and the classical well-known pathways of activation, namely, the CD3/TCR and CD2 pathways. Competitive blocking experiments were performed in which the effects of monoclonal antibodies (MAb) to the CD3/TCR complex or to the CD2 molecule were evaluated on the HTLV-I activation of T cells and compared with that obtained on phytohemagglutinin (PHA)-stimulated cells. It was found that anti-CD3 or -TCR MAb strongly suppress the proliferative response of T cells to PHA, but are significantly less efficient in inhibiting the activation initiated by HTLV-I. By contrast, MAb recognizing specific epitopes of the CD2 molecule inhibit the proliferative response of T cells to PHA or to HTLV-I to the same extent. The results provide evidence that HTLV-I virions interfere mainly with activation via CD2 but not via the CD3/TCR complex. Considering the earlier expression of the CD2 molecule on human T-cell precursors, these observations might be relevant to the characterization of the differentiation stage at which viral infection could interfere with the development and the maturation of T lymphocytes.
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PMID:Peripheral T-lymphocyte activation by human T-cell leukemia virus type I interferes with the CD2 but not with the CD3/TCR pathway. 257 39

The effects of 1,25(OH)2D3 and dexamethasone on cellular proliferation and gene expression of the HTLV-I-infected T-cell line, KH-2, established from a patient with adult T-cell leukemia, endemic in the south-west Japanese islands and the Caribbean, were examined. KH-2 cells are integrated by HTLV-I proviral DNA and expressed mRNA for c-myc, IL-2 receptor alpha-chain (IL-2R alpha), and T-cell receptor beta-chain (TCR beta) while it did not express IL-2 mRNA. 1,25(OH)2D3 and dexamethasone did not suppress the mRNA levels of HTLV-I, IL-2R alpha or TCR beta but reduced the c-myc mRNA level. The reduction of c-myc mRNA level was marked in 1,25(OH)2D3-treated cells but relatively weak in dexamethasone-treated cells. This inhibitory effect of the steroid hormones correlated with the inhibition of KH-2 cell proliferation.
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PMID:Suppression of c-myc mRNA expression by steroid hormones in HTLV-I-infected T-cell line, KH-2. 279 41

The early event of thymocyte maturation has been analyzed using acute lymphoblastic leukemia (ALL) cells. A group of ALL cells whose cell surface phenotype was CD2 (SRBC receptor) negative and CD7 (T cell antigen) positive has been considered as precursor thymocyte ALL (pre-T-ALL). No rearrangements of the T cell receptor beta-gene (TCR beta) and gamma-gene (TCR gamma) were found in three of four pre-T-ALL patients. Stimulation of these pre-T-ALL cells with 12-0-tetradecanoylphorbol-13-acetate (TPA) induced only CD25 (Tac) antigen but no other T cell antigens. These findings suggest that the activation pathway of interleukin 2 (IL-2) receptor already exists in the most immature precursor thymocytes. Pre-T-ALL cells from the fourth patients showed the expression of CD3 antigen, and both TCR beta and TCR gamma rearrangement. TPA induced the differentiation of the more mature pre-T-ALL cells of this case in vitro, and not only CD25 (Tac) antigen but also CD4 and CD8 antigens appeared on the cell surface. The low affinity binding of 125I-IL-2 to TPA-stimulated leukemia cells was observed in the three cases of pre-T-ALL tested, and the addition of recombinant IL-2 to TPA-stimulated cells showed no effect on cell proliferation.
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PMID:Phorbol ester induces interleukin-2 receptor on the cell surface of precursor thymocyte leukemia with no rearrangement of T cell receptor beta and gamma genes. 282 68

Specimens from 19 patients with NHL were also phenotyped at the onset of the disease; among them, 9 were studied in the relapse phase. The analysis was carried out with monoclonal antibodies directed against T and myeloid cells; at diagnosis, all cases presented an immature thymic phenotype. When analyzed at relapse, phenotypic changes were observed: intra-lineage dedifferentiations (6 cases); mixed-lineage lymphoid and myeloid (2 cases), and pure myeloid relapses (1 case). The molecular analysis of the TCR-genes configuration showed a germ-line pattern at onset and relapse in Case 9 and a modification of the rearrangement patterns during the evolution of the disease in Case 6. These data point out that the relapse is often accompanied by intra-lineage modifications resembling dedifferentiation and, more rarely by a myeloid switch. The phenotypic follow-up of these patients may be important to the implementation of chemotherapeutic protocols that are more adequate for the biological evolution of the disease.
Leukemia 1988 Dec
PMID:Mixed-lineage leukemias and phenotypic shifts occurring in relapsed cases of acute T lymphoblastic lymphomas. 284 96

Lymphoid tumors induced by a recombinant murine retrovirus carrying the v-myc oncogene of avian MC29 virus were characterized. The Moloney murine leukemia virus myc oncogene (M-MuLV (myc], carried by an amphotropic MuLV helper, induced tumors in NIH Swiss and NFS/N mice after a relatively long latency (8 to 24 wk). Tumor masses appeared in the thymus, spleen, and lymph nodes. Flow cytometry of the tumor cells indicated that approximately 50% were positive for Thy 1.2. Most of these tumors also expressed one or more other cell surface markers of thymocytes and mature T cells (CD4, CD8). Southern blot hybridization revealed genomic rearrangements for the TCR beta genes. The TCR beta analysis suggested that the M-MuLV(myc)-induced Thy 1.2+ tumors were derived from somewhat less mature cells than tumors induced by M-MuLV, which is a classical non-acute retrovirus lacking an oncogene. The remainder of the M-MuLV(myc)-induced tumors were Thy 1.2-, but they were positive for Ly-5 (B220) and also for MAC-2. The Thy 1.2- tumors were characteristically located in the thymus. However, they were negative for TCR beta gene rearrangements. Some, but not all, of the Thy 1.2- tumors contained rearrangements for Ig genes. Additionally, they typically expressed mRNA specific for B but not for T cells. Thus, these thymic tumors had characteristics of the B cell lineage. Tumor transplantation experiments demonstrated that the Thy 1.2- tumor cells could reestablish in the thymus and spleen of irradiated hosts, and low level expression of the Thy 1 molecule was observed in the thymus but not the spleen on the first passage. After serial passage, one Thy 1- tumor altered its cell surface phenotype to Thy 1low B220-.
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PMID:Characterization of lymphoid tumors induced by a recombinant murine retrovirus carrying the avian v-myc oncogene. Identification of novel (B-lymphoid) tumors in the thymus. 290 39


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