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1.
Haran-Ghera N 《Nature: New biology》1972,238(79):21-23
IN C57BL/6 mice, infection with the radiation leukaemia virus is age dependent and leukaemogenesis is highly effective only when the virus is inoculated shortly after birth1,2, but several months elapse before the disease is actually manifested. Why is there such a long latent period before the leukaemic cells proliferate into a palpable tumour, especially as in the newborn mouse the target organ for the development of the disease, the thymus, is still in a proliferative stage, with abundance of immature lymphoid cells and an incompetent immunological system? 相似文献
2.
Functional cell compartments were studied in a rat model for human acute myelocytic leukaemia (AML). This was done by tracing the distribution of injected 51Chromium-labelled leukaemic cells in the body. It was concluded that two functional compartments can be distinguished in acute leukaemia, i.e., a rapidly exchangeable pool of cells (including the circulating blood pool, the marginal noncirculating blood pool and the rapidly exchangeable tissue pool; RETP) and a slowly exchangeable tissue pool (SETP). The sizes of these various compartments were roughly quantified at various stages of the disease by calculations based on the principle of isotope dilution and organ weight measurements. As the leukaemia progresses, the size of the SETP increases significantly relative to the size of the RETP. Simultaneously, the exchange rates of leukaemic cells between the organs and the blood decrease. The blood transit time of leukaemic cells was also significantly prolonged, as is the case in human AML. 相似文献
3.
A. M. E. Nouri E. Dorey C. L. Davis A. Rohatiner T. A. Lister R. T. D. Oliver 《Cancer immunology, immunotherapy : CII》1993,37(1):47-53
Peripheral blood mononuclear cells from 13 patients with acute leukaemia were used to establish long-term interleukin-2-dependent cytotoxic T lymphocytes. Cells were grown in RPMI medium containing interleukin-2 (IL-2, 100 U/ml) and 2.5% conditioned medium prepared by activating normal lymphocytes with phytohaemagglutinin. Proliferation of IL-2-dependent CD3-positive lymphocytes was seen in 1 of 2 acute lymphocytic leukaemia cases (ALL), 1 of 4 acute myelogeneous leukaemia cases (AML) (M1) and 8 of 8 more differentiated AML. In 2 cases with detectable leukaemic cell markers (1 ALL and 1 AML) passageable cells were developed, that expressed normal T cell phenotypes (namely CD3, CD4, and CD8) at the expense of leukaemic cells. In 1 of 2 cases, long-term IL-2-cultured cells showed specific cytotoxic activity against autologous leukemic cells. The percentage killing against autologous and two allogeneic target cell lines at a 50/1 effector/target (E/T) ratio was 42%, 9% and 19% respectively. Similarly the cytotoxic activity of IL-2 activated from 4 different individuals against conventional tumour targets K562 and Daudi at a ratio of 50/1 was 29%–68% (median=55%) and 34%–78% (median=61%) respectively. It was also found that this killing potential of the activated cells was maintained for as long as culture was continued (median 23 days, range 17–75 days). The mechanism(s) of T cell proliferation at the expense of leukaemic blast cells in the case of a minority of leukaemic patients and the possible clinical therapeutic potential of these cells following in vitro IL-2 activation deserve further investigation. 相似文献
4.
Kun Li Wenfu Xu Ke Lu Yuxi Wen Tianqing Xin Yaqing Shen Xueyan Lv Shimin Hu Runming Jin Xiaoyan Wu 《Journal of cellular and molecular medicine》2020,24(22):13115
Research in the last few years has revealed that leukaemic cells can remodel the bone marrow niche into a permissive environment favouring leukaemic stem cell expansion. Tumour‐associated macrophages (TAMs) are prominent components of the tumour microenvironment and play an important role in the onset and progression of solid tumours. However, little is known about their role in the development of acute lymphoblastic leukaemia (ALL). Using a unique mouse model of T‐ALL induced by injection of EL4 T‐cell lymphoma cells to syngeneic C57BL/6 mice, we report herein that ALL leads to the invasion of leukaemia‐associated monocyte‐derived cells (LAMs) into the bone marrow and spleen of T‐ALL mice. Furthermore, we found that leukaemia cells could polarize bone marrow–derived macrophages (BMDMs) into LAMs. In turn, LAMs were able to protect leukaemia cells from drug‐induced apoptosis in vitro. Therapies targeted against the TAMs by inhibiting colony stimulating factor‐1 receptor (CSF‐1R) have emerged as a promising approach for cancer treatment. In this study, we demonstrate that CSF‐1R inhibition inhibits the viability of BMDMs, blocks LAMs polarization and reduces the abundance of LAMs in T‐ALL mice. In vivo, combination treatment of CSF‐1R inhibitor and vincristine (VCR) dramatically increased the survival of T‐ALL mice and delayed leukaemia progression compared with VCR monotherapy. Finally, these data reinforce the role of microenvironments in leukaemia and suggest that macrophages are a potential target for the development of novel therapeutic strategies in T‐ALL. 相似文献
5.
6.
Leonie K. Ashman Denise E. O'Keefe Christopher A. Juttner R. G. Toogood Michael S. Rice 《Cancer immunology, immunotherapy : CII》1986,22(2):95-99
Summary Cryopreserved leukaemic blasts and remission non-T cells from 22 patients with acute leukaemia (15 lymphocytic, 7 non-lymphocytic) were tested as stimulators of autologous remission T cells and normal allogeneic T cells in primary and secondary MLC. In most cases the autologous response elicited by leukaemic cells was less than or equal to that elicited by remission non-T cells. However, T cells from 2 patients in long-standing first remission from ANLL displayed greater proliferation in response to leukaemic blasts than to remission non-T cells in both primary and secondary MLC. The results are suggestive of sensitization of these 2 patients to leukaemia-specific antigens, but other possible explanations are discussed.
Abbreviations used: MLC, mixed leucocyte culture; ANLL, acute non-lymphocytic leukaemia; ALL, acute lymphoblastic leukaemia; AMLR, autologous mixed lymphocyte reaction; NK cells, natural killer cells; MNC, mononuclear cells 相似文献
7.
T cell clones (CD4+CD8–TCRαβ+γδ–) derived from bone marrow transplant recipients were stimulated with phytohaemagglutinin (PHA) +interleukin-2 (IL-2) in the
presence of irradiated (50 Gy) peripheral blood mononuclear cells (PBMC) derived from acute leukaemia patients(leukaemic PBMC
containing more than 95% blast cells). Leukaemic PBMC could function as accessory cells during mitogenic T cell activation
resulting in both T cell proliferation and a broad T cell cytokine response [IL-3, IL-4, IL-10, granulocyte/macrophage-colony-stimulating
factor (GM-CSF) tumour necrosis factor α (TNFα) and interferon γ (IFNγ) secretion]. Blockade of IL-1 effects by adding IL-1
receptor antagonist together with PHA+IL-2+leukaemia blasts increased T cell proliferation, whereas IL-6-neutralizing antibodies
did not alter T cell proliferation. A qualitatively similar T cell cytokine response and a similar cytokine profile (highest
levels detected for GM-CSF and IFNγ) were detected when normal polyclonal T cell lines were stimulated with PHA in the presence
of non-irradiated leukaemic PBMC. When leukaemic PBMC derived from 18 acute myelogenous leukaemia patients were cultured with
PHA and cells from a polyclonal T cell line, increased concentrations of the T cell cytokines IFNγ and IL-4 were detected
for all patients. We conclude that T cell activation resulting in proliferation and a broad cytokine response can take place
in the presence of excess acute myelogenous leukaemia blasts.
Received: 30 November 1995 / Accepted: 9 January 1996 相似文献
8.
K Koubek 《Folia haematologica (Leipzig, Germany : 1928)》1982,109(3):408-415
Some sera from normal donors (1/18) and from leukaemic patients (2/7 with acute myeloid leukaemia [AML], 1/4 with chronic lymphatic leukaemia [CLL], 0/3 with acute lymphoblastic leukaemia [ALL]; with high numbers of leukaemic cells expressing Ia-like p28,33 antigen on the leukaemic cell surface) inhibited the complement mediated cytotoxic activity of highly specific xenogenous anti Ia-like sera (which were prepared by immunization of rabbits with insoluble membrane fractions of B-type lymphoid lines) at a titre 1:4 or less. This effect was not observed with antisera directed against other membrane marker determinants (e.g. T lymphocyte specific antigens). These results suggest that at least a small proportion of membrane bound Ia-like antigens can be released from cell surfaces and in some patients these Ia-like moieties are detectable (by sensitive inhibition assays) in the serum. 相似文献
9.
Streptovaricins inhibit Focus Formation by MSV (MLV) Complex 总被引:9,自引:0,他引:9
We recently reported that the streptovaricins inhibit the reaction by which DNA is transcribed from the RNA template resident in murine leukaemia virions (MLV)1. The reports2, 3 which first indicated that this DNA polymerase is present in oncogenic RNA viruses have been confirmed and extended4–8. The enzyme provides a mechanism whereby an RNA virus can insert stable genetic information into a host chromosome. Gallo and co-workers described an RNA dependent DNA polymerase in lymphoblastic leukaemic cells which was inhibited by N-demethylrifampicin9 and this antibiotic, together with a number of other rifamycin derivatives, also inhibited the oncogenic viral DNA polymerase10. Like the streptovaricins, the rifamycins are ansa macrolide antibiotics (Fig. 1). 相似文献
10.
11.
Defective Friend Spleen Focus-forming Virus: Pseudotype Neutralization by Helper-specific Antisera 总被引:3,自引:0,他引:3
SINCE its isolation in Swiss mice in 1956, Friend virus1 (FV) has been regarded as a single viral entity. Recently, however, it has been recognized in several laboratories that FV stocks contain at least two distinct viruses2–4, which we have named—on the basis of their pathogenic properties—spleen focus-forming virus (SFFV) and lymphatic leukaemia virus (LLV)4. The onset of the disease induced by SFFV is rapid; 9 days after inoculation of susceptible adult mice discrete focal lesions appear in the splenic red pulp and shortly afterwards the mice develop hepatosplenomegaly, erythroblastosis and, with some virus isolates, polycythaemia5. In contrast, LLV isolated free of detectable SFFV4 and injected intraperitoneally into susceptible newborn mice takes 6–12 weeks to induce lymphatic leukaemia, principally in the spleen, but with leukaemic infiltration extending to abdominal and peripheral lymph nodes, liver and thymus (unpublished observations of R. A. S. and E. A. Mirand). Virus titres of LLV stocks are usually greater than 104 ID50/ml.6, in the same order of magnitude as SFFV (in focus forming units/ml.) in the original FV preparations. 相似文献
12.
Bin Zhou Yaqian Qin Jingying Zhou Jichen Ruan Fang Xiong Jinglai Dong Xingzhou Huang Zhijie Yu Shenmeng Gao 《Journal of cellular and molecular medicine》2021,25(6):3124-3135
Acute myeloid leukaemia (AML) with chromosomal rearrangements involving the H3K4 methyltransferase mixed-lineage leukaemia (MLL) is an aggressive subtype with low overall survival. Bortezomib (Bort) is first applied in multiple myeloma. However, whether bort possesses anti-self-renewal and leukemogenesis of leukaemia stem cell (LSC) in AML with MLL rearrangements is still unclear. Here, we found that bort suppressed cell proliferation and decreased colony formation in human and murine leukaemic blasts. Besides, bort reduced the frequency and function of LSC, inhibited the progression, and extended the overall survival in MLL-AF9 (MF9) -transformed leukaemic mice. Furthermore, bort decreased the percentage of human LSC (CD34+CD38-) cells and extended the overall survival in AML blasts-xenografted NOD/SCID-IL2Rγ (NSG) mice. Mechanistically, cyclin dependent kinase 6 (CDK6) was identified as a bort target by RNA sequencing. Bort reduced the expressions of CDK6 by inhibiting NF ĸB recruitment to the promoter of CDK6, leading to the abolishment of NF ĸB DNA-binding activity for CDK6 promoter. Overexpression of CDK6 partially rescued bort-induced anti-leukemogenesis. Most importantly, bort had little side-effect against the normal haematological stem and progenitor cell (HSPC) and did not affect CDK6 expression in normal HSPC. In conclusion, our results suggest that bort selectively targets LSC in MLL rearrangements. Bort might be a prospective drug for AML patients bearing MLL rearrangements. 相似文献
13.
Sanchez-Correa B Morgado S Gayoso I Bergua JM Casado JG Arcos MJ Bengochea ML Duran E Solana R Tarazona R 《Cancer immunology, immunotherapy : CII》2011,60(8):1195-1205
Natural killer (NK) cell activation is strictly regulated to ensure that healthy cells are preserved, but tumour-transformed
or virus-infected cells are recognized and eliminated. To carry out this selective killing, NK cells have an ample repertoire
of receptors on their surface. Signalling by inhibitory and activating receptors by interaction with their ligands will determine
whether the NK cell becomes activated and kills the target cell. Here, we show reduced expression of NKp46, NKp30, DNAM-1,
CD244 and CD94/NKG2C activating receptors on NK cells from acute myeloid leukaemia patients. This reduction may be induced
by chronic exposure to their ligands on leukaemic blasts. The analysis of ligands for NK cell-activating receptors showed
that leukaemic blasts from the majority of patients express ligands for NK cell-activating receptors. DNAM-1 ligands are frequently
expressed on blasts, whereas the expression of the NKG2D ligand MICA/B is found in half of the patients and CD48, a ligand
for CD244, in only one-fourth of the patients. The decreased expression of NK cell-activating receptors and/or the heterogeneous
expression of ligands for major receptors on leukaemic blasts can lead to an inadequate tumour immunosurveillance by NK cells.
A better knowledge of the activating receptor repertoire on NK cells and their putative ligands on blasts together with the
possibility to modulate their expression will open new possibilities for the use of NK cells in immunotherapy against leukaemia. 相似文献
14.
Rao Q Wang JY Meng J Tang K Wang Y Wang M Xing H Tian Z Wang J 《Cell biology international》2011,35(9):945-951
E-cadherin (epithelial cadherin) belongs to the calcium-dependent adhesion molecule superfamily and is implicated in the interactions of haematopoietic progenitors and bone marrow stromal cells. Adhesion capacity to bone marrow stroma was impaired for leukaemia cells, suggesting that a breakdown of adhesive mechanisms governed by an adhesion molecule may exist in leukaemic microenvironment. We previously found that E-cadherin was low expressed in primary acute leukaemia cells compared with normal bone marrow mononuclear cells. In this study, we investigate the functional importance of low E-cadherin expression in leukaemia cell behaviours and investigate its effects in the abnormal interaction of leukaemic cells with stromal cells. After expression of E-cadherin was restored by a demethylating agent in leukaemia cells, E-cadherin-specific adhesion was enhanced. Additionally, siRNA (small interfering RNA)-mediated silencing of E-cadherin in Raji cells resulted in a reduction of cell homophilic adhesion and enhancement of cell proliferation and colony formation. These results suggest that low expression of E-cadherin contributes to the vigorous growth and transforming ability of leukaemic cells. 相似文献
15.
Serological Identification of Hamster Oncornaviruses 总被引:12,自引:0,他引:12
ROBERT C. NOWINSKI LLOYD J. OLD PAUL V. O'DONNELL F. KINGSLEY SANDERS 《Nature: New biology》1971,230(17):282-284
CATS, mice and chickens have indigenous oncornaviruses (oncogenic RNA viruses) which induce leukaemias and sarcomas1,2. Mouse sarcoma virus (MuSV), like avian sarcoma virus, can induce sarcomas in the hamster3,4 but some of these MuSV hamster sarcomas release virus that differs both antigenically and with regard to its host range from the original5—it can be neutralized by antisera prepared against isolates of virus released from MuSV-transformed cells but not by antisera against murine leukaemia virus (MuLV) and it is sarcomagenic in hamsters but not in mice. Such a virus could be: (a) an indigenous hamster sarcoma virus “activated” by the inoculation of MuSV; (b) an MuSV genome that has acquired a new viral envelope from an indigenous hamster leukaemia virus (HaLV) during its sojourn in hamsters; or (c) a recombinant between HaLV and the sarcomagenic portion of the MuSV genome. In fact, it is known that the hamster possesses a virus (HaLV) which is morphologically similar to MuLV6,7. This virus lacks8 the group-specific (gs) internal MuLV-gs1 antigen characteristic of MuLV9,10 although it does have the gs antigen (MuLV-gs3) which is common to all mammalian leukaemia viruses investigated so far8. 相似文献
16.
Functional cell compartments were studied in a rat model for human acute myelocytic leukaemia (AML). This was done by tracing the distribution of injected 51Chromium-labelled leukaemic cells in the body. It was concluded that two functional compartments can be distinguished in acute leukaemia, i.e., a rapidly exchangeable pool of cells (including the circulating blood pool, the marginal noncirculating blood pool and the rapidly exchangeable tissue pool; RETP) and a slowly exchangeable tissue pool (SETP). The sizes of these various compartments were roughly quantified at various stages of the disease by calculations based on the principle of isotope dilution and organ weight measurements. As the leukaemia progresses, the size of the SETP increased significantly relative to the size of the RETP. Simultaneously, the exchange rates of leukaemic cells between the organs and the blood decrease. The blood transit time of leukaemic cells was also significantly prolonged, as is the case in human AML. 相似文献
17.
The behaviour of normal haemopoietic stem cells of the bone marrow during the development of the acute transferable rat leukaemia, L 5222, has been investigated. The granulopoietic committed stem cells, measured by the in vitro colony technique, showed a marked decrease to less than half normal levels. Pluripotent stem cells included in the small lymphocytes of the bone marrow, and labelled with 3H-thymidine by the complete labelling method, showed only a modest decrease in number and an unchanged labelling intensity. The results suggest that in this leukaemia the pluripotent stem cells may be affected in such a way that they are unable to react by proliferation to the depletion of the succeeding cell compartments. This might be due to inhibition by leukaemic cells or to a disturbed feedback regulation between the committed and pluripotent stem cell compartments. 相似文献
18.
K Schneiberg K Rytwiński W Bartnikowa 《Folia haematologica (Leipzig, Germany : 1928)》1976,103(6):852-859
In mice vaccinated with two forms of lymphoblastic leukaemia and alkalized with intravenous administration of sodium bicarbonate, the survival rate, the extent of leukaemic infiltration and the proliferative capacity of cells in the bone-marrow, thymus, spleen, lymphnodes, liver and lungs were investigated. The survival rate in the TAL leukaemia of the AKR stem producing an endogenous acidosis could be significantly prolonged in a statistical way by alkalization. Yet an accelerated expiring rate could be observed after exogenous alkalization in L-1210 leukaemia of the DBA/2J stem producing an endogenous alkalosis. By means of cytological and impulse-cytophotometrical investigations the exogenous alkalization of both forms of leukaemia could be proved to have a direct bearing on the proliferative kinetics. In TAL leukaemia the leukaemic proliferation was inhibited by the exogenously involved correction of the acid-base balance; in the L-1210 leukaemia, however, the pH disturbances were enhanced, thus accelerating the leukaemic proliferation. Consequently, the disturbances of the acid base balance seem to be an essential cofactor in the leukaemia genesis. The exogenous direction of the acid-base balance may be important as a means of treating leukaemia. 相似文献
19.
Jozef Hatok Tatiana Matáková Juraj Chudej Ján Sta?ko Miroslava Dobrotová Du?an Dobrota Peter Ra?ay 《Biologia》2009,64(1):203-207
The fact that leukaemic cells are primarily or secondarily resistant to cytostatics is a serious phenomenon, which leads to
the failure of chemotherapy of malignant diseases in clinical practise. Some detoxification and transporting systems are responsible
for the generation of chemoresistance on the cellular level and the decrease of effectiveness in treatment. In vitro testing of chemoresistance of leukaemic cells is presently an inseparable component of “tailoring” therapy in the developing
field of predictive oncology. The aim of this work was to estimate profiles of drug resistance, based on the predictive in vitro test, and to help in choosing the most effective cytostatic. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoline (MTT)
assay was used, based on the direct effect of cytostatics on the viability of leukaemic cells in vitro. The number of living leukaemic cells was evaluated by a computer program, where LC50 (concentration of cytostatics lethal to 50% of leukaemic cells) was established from the achieved dose-relation curves. Seventy-one
samples of leukaemic cells isolated from the patients’ peripheral blood or bone marrow were examined. All samples were tested
to 3 cytostatics minimally. It was found by the in vitro assay, that resistance to dexamethasone, prednisolone, etoposide and vincristine is increased in patients with acute myeloid
leukaemia disease, compared to the acute lymphoblastic leukaemia patients. In patients with a relapsed disease population,
leukaemic cells are highly heterogeneous in the MTT assay. It was concluded that the MTT assay can be used to study drug interactions
in vitro in leukaemia samples. The type of interaction was highly different between patients, and depended on drug concentrations. 相似文献
20.
F D Tóth L Váczi M Kása T Karsai 《Acta microbiologica Academiae Scientiarum Hungaricae》1976,23(2):185-190
The serum of Balb/c mice infected with Rauscher leukaemia virus contained soluble antigens characterized by alpha2 and beta globulin electrophoretic mobility; their respective molecular weights, as determined with gel filtration, were 40 000 and 120 000. The antigens differed in specificity and their corresponding determinants were present on the surface of leukaemic cells. For Balb/c mice both antigens, for DBA/1 and C57B1/10Sn mice only the antigen showing alpha2 mobility was immunogenic. 相似文献