Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spontaneous expression of endogenous N- and B-tropic murine leukemia viruses was stu1bb), DDD (Fuv-1nn), DDD-Fvr (fv-1nn), (DDD or DDD-Fvr times C57BL/6)F1, and 16 partially inbredlines with either the Fv-1nn or Fv-1bb genotype, which had been established from hybrids between C57BL/6 and DDD-Fvr. When tested at middle age, virus-positive mice were found in C57BL/6, F1 hybrids, and 9 out of 16 partially inbred lines. N-tropic viruses were isolated from Fv-1nn, Fv-1bb mice, whereas B-tropic viruses, except for one isolate, were from Fv-1bb mice only. C57BL/6 mice were positive for both N- and B-tropic viruses, whereas DDD-Fvr mice were negative. With respect to the Fv-1 genotype and the presence of endogenous murine leukemia viruses, the partially inbred lines were grouped into five types: (i) Fv-1bb, both N- and B-tropic virus positive, like C57BL/6; (ii) Fv-1nn, virus negative, like DDD-Fvr; (iii) Fv-1bb, virus negative; (iv) Fv-1nn, only N-tropic virus positive; and (v) less convincingly, Fv-1bb, only B-tropic virus positive. These findings indicate that the transmission of N- and B-tropic viruses in C57BL/6 is genetically controlled and that the expression of B-tropic virus, but not of N-tropic virus, is closely associated with the Fv-1 genotype.
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PMID:Genetic transmission of endogenous N- and B-tropic murine leukemia viruses in low-leukemic strain C57BL/6. 16 59

We observed a marked discordance between in vivo and in vitro sensitivities to Friend murine leukemia virus in G mice. In vivo resistance of G mice was more than 10(5)-fold relative to sensitive DDD mice, whereas in vitro resistance was only 50 to 100-fold. In vivo sensitivity to N- and NB-tropic Friend murine leukemia virus was recessive in (G X DDD)F1 mice, whereas in vitro sensitivity was dominant in the heterozygotes. The resistance of mouse fibroblasts was different from the resistance of fibroblasts of a certain NZB mouse strain.
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PMID:Resistance of G mice to murine leukemia virus infection: apparent disparity in in vivo and in vitro resistances. 27 31

A transplantable mouse T cell leukemia, DL 812, is characterized by high sensitivity to 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-chloroethyl)-1-nitrosourea hydrochloride (ACNU) and intensive systemic infiltration. When subcutaneously inoculated, DL812 cells invade many organs and cause marked splenomegaly without forming local tumors. Disseminated DL812 leukemias are clinically completely cured by a single intraperitoneal injection of 1 mg ACNU, but more ACNU-resistant leukemias relapse immediately. A novel antitumor antibiotic, spergualin, is effective against various mouse leukemias. The effects of its analog with stronger anti-leukemia activity, 15-deoxyspergualin (DSG), on the relapse of DL812 leukemias after ACNU treatment were investigated. DDD mice were subcutaneously inoculated with 10(6) DL812 cells and intraperitoneally injected with 1 mg ACNU once on day 11 and with 100 micrograms DSG daily from day 12 on. The relapses were clinically completely suppressed for at least 30 days. Winn assays with spleen cells revealed that host immunity did not play a major role in maintenance of the clinical cure. Thus, when DSG treatment was discontinued after 15 or 30 daily injections, leukemias relapsed immediately. When it was extended to 50 daily injections, permanent cure was attained in 1 of 15 mice but relapses occurred under DSG treatment in the others. DSG is available for combined treatment of the leukemia. The current and previous results suggest that DL812 leukemias may serve as a model in study on immunochemotherapy of the disease.
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PMID:Spergualin treatment-dependent delayed relapse of mouse T cell leukemia (DL812) after chemotherapy. 179 66

The B-cell leukemia line, DL811, established in DDD mice, has been characterized by strong immunogenicity leading to occasional spontaneous cure with tumor dormancy. Cyclophosphamide (CY) is an available chemo-immunotherapeutic agent. The effects of CY on the cure and dormancy of DL811 leukemias were investigated. Simultaneous injection of DL811 cells and CY into athymic nude mice revealed that DL811 cells were sensitive to CY doses of 0.5 mg and more per mouse in a dose-related manner. A single dose of 1 mg CY on day 7 after DL811 cell inoculation was most curative of disseminated leukemias (cure rate: 50-80%) as compared with other single CY doses at different times. Cured mice were strongly immune to DL811 leukemias. This therapeutic modality had no curative effect in athymic nude mice. Relapses occurred occasionally in CY-cured mice and most relapsed tumors had the same surface phenotype as that of the DL811 leukemia. In comparison with DL811 leukemias, however, relapsed tumors were less sensitive to rejection by cured mice and less frequently cured by a single dose of 1 mg CY on day 7 of inoculation, implying that they changed in antigenicity and drug sensitivity. Whole-body irradiation of 400 rad gamma-rays to cured mice raised the incidence of relapses from 22.9 to 44.7% and that of deaths from relapses from 8.6 to 26.3%. Thus, leukemic cells may survive against host immune surveillance in a dormant state and relapse after changing their immunologic and chemotherapeutic natures. Lyt-2+, L3T4- T cells appeared to mediate host anti-tumor immunity to eradicate leukemic cells and maintain dormant state.
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PMID:Survival of leukemic cells in a dormant state following cyclophosphamide-induced cure of strongly immunogenic mouse leukemia (DL811). 187 74

The strongly immunogenic B-cell leukemia line, DL811, was established from a spontaneous leukemia in DDD mice. When 10(6) DL811 cells were s.c. inoculated, all athymic DDD-nu/nu mice died of disseminated leukemia but less than 20% of euthymic DDD mice were spontaneously cured of it. Although cured mice resisted a challenge with 10(7) DL811 cells, they frequently died of relapse. Whole-body gamma-ray irradiation accelerated the relapse of leukemias, implying that leukemic cells can survive against host immune cell killing in a dormant state. L3T4+ Lyt-2+ T cells were suggested to have a significant role in spontaneous cure and maintenance of the dormant state.
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PMID:Characterization of a strongly immunogenic mouse leukemia line (DL811) undergoing spontaneous cure with tumor dormancy. 204 84

A group of retroviruses carrying truncated viral genes has recently been suggested as the cause of new patterns of diseases. One such virus is the replication defective component of the Friend murine leukemia virus (F-MuLV) complex, called Friend spleen focus forming virus (F-SFFV). This virus induces erythroblastosis, and a virion envelope-related glycoprotein, gp55, encoded by F-SFFV has been suggested as the pathogenic gene. The role of the gp55 gene is, however, yet unclear in the apparently multistep erythroleukemogenesis. By separately producing transgenic mice harboring the whole F-SFFV DNA, the gp55 gene alone under the control of the retroviral long terminal repeat (LTR) and the gp55 gene under the control of cytoplasmic beta actin transcriptional regulatory unit, we show here that the gp55 gene is capable of inducing neoplastic proliferation of erythroid progenitor cells specifically in the absence of helper virus and other F-SFFV sequences. Under the control of the viral LTR the gp55 expression was detected only in leukemic tissues, but under the control of cytoplasmic beta-actin regulatory sequences, the gp55 was also expressed in a variety of normal tissues including preleukemic normal spleens. The development of erythroleukemia was suppressed under the genetic background of C57B1/6 mouse (resistant to F-MuLV; Fv-2rr), and required additional events even under the background of DDD mouse (susceptible to F-MuLV; Fv-2ss). The p53 and Spi-1 genes were frequently aberrant in transplanted tumors and cell lines derived from them, but were not in primary leukemic spleens.
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PMID:Env-derived gp55 gene of Friend spleen focus-forming virus specifically induces neoplastic proliferation of erythroid progenitor cells. 216 63

Seven transplantable leukemia lines were established from spontaneous leukemias and screened for 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(chloroethyl)-1-nitrosourea hydrochloride (ACNU) sensitivity in DDD mice. Three of them were classified as highly sensitive, two as sensitive and two as resistant to ACNU. A highly sensitive line, DL812, was extensively characterized from a therapeutic point of view. DL812 cells were so invasive as to produce enlargement of spleens and lymph nodes but not local tumors when injected s.c., markedly sensitive to in vitro ACNU exposure and moderately immunogenic. The invasion process of DL812 cells differed with the status of host immunity. Advanced DL812 leukemias were macroscopically completely cured with normalization of spleen and lymph node sizes 3-7 days after an i.p. injection of 0.5 mg ACNU, but more ACNU-resistant leukemias with splenomegaly and enlarged lymph nodes recurred thereafter. Recurring DL812 cells were approximately four times more resistant to in vitro ACNU exposure but maintained similar immunogenicity as compared to the original ones. Permanent cures of advanced leukemias were achieved by ACNU treatment plus subsequent adoptive transfer of immune splenocytes in 15% of diseased mice. The results suggest the importance of host antitumor immunity for permanent cures of highly drug-sensitive leukemias, overcoming drug resistance and relapse.
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PMID:Importance of antitumor immunity for complete cure of highly drug-sensitive leukemia in mice. 275 24

The hematopoietic disregulation in adult mice induced by the malignant histiocytosis sarcoma virus (MHSV) and the Harvey murine sarcoma virus (Ha-MuSV), which both possess c-Ha-ras-related oncogenic sequences, was investigated. Spleen focus formation induced by MHSV and Ha-MuSV was not restricted by the Fv-2 resistance locus in congenic DDD and C57BL/6 mice, unlike leukemogenesis induced by Friend virus, Rauscher virus, and the myeloproliferative sarcoma virus (MPSV). C57BL/6 mice were much more resistant to MHSV and Ha-MuSV-induced spleen focus formation than DDD mice regardless of their Fv-2 state. Infection of DDD mice with MHSV caused a systemic histiocytic neoplasia, best described as murine malignant histiocytosis. Transformed histiocytic cells proliferated excessively in the bone marrow, spleen, and lymph nodes and, in the final stages of the disease, in all major parenchymal organs. The Ha-MuSV caused a strikingly different benign histiocytic tumor in DDD mice and, unlike MHSV, did not induce a rapid, progressive splenomegaly in C57BL/6 mice. Infection of DDD mice with MHSV induced a rapid and synchronized depletion of early and late erythroid precursor cell pools. In MHSV-infected C57BL/6 mice comparable changes were observed with dissimilar kinetics. Macrophage colony-forming cells of MHSV-infected mice were increased in number and proliferated independently of stimulating growth factors. The disease induced by MHSV in mice can thus serve as a model for malignant histiocytosis in humans.
Leukemia 1987 Jan
PMID:Murine retrovirus-induced malignant histiocytosis, an experimental model for the disease in humans. 282 12

Formation of proviral DNAs by B-tropic murine leukaemia viruses (MLVs) was examined in N-type and dually permissive mutant cells derived from two inbred mouse strains, DDD and G, both of which are N-type. In the N-type cells, formation of circular proviral DNA was strongly suppressed relative to that of linear DNA. Mutation resulting in loss of the N-type Fv-1 restriction resulted in efficient formation of circular DNA by the previously restricted B-tropic MLV. This showed that Fv-1 restriction and inhibition of closed circular DNA formation were controlled by the same gene. The efficiency of formation of circular proviral DNA by the defective Kirsten murine sarcoma virus was determined by the tropism of the helper virus.
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PMID:Synthesis of proviral DNA in inbred mouse-derived clones of cells expressing different Fv-1 phenotypes. 299 62

Two newly established mouse strains which are congenic with standard inbred strains were used for the study of the locus Fv which controls the susceptibility to Friend leukemia virus in mice. A strain in each congenic pair shares the major histocompatibility gene with the corresponding partner strain but differs from the latter in the Fv locus. Mice with Fv(r)/Fv(r) genotype (DDD-Fv(r), C57BL/6) do not develop marked spleen enlargement upon virus challenge, whereas spleens of mice with Fv(s)/Fv(s) genotype (DDD, C57BL/6-Fv(s)) become large even with a virus inoculum 1/10(3) to 1/10(5) times that used for the resistant strains. Mice of each strain were heavily irradiated, inoculated with bone marrow cells taken from either syngenic or corresponding congenic mice, and challenged later with the leukemia virus. When Fv(s)/Fv(s) mice had been restored with bone marrow cells taken from Fv(r)/Fv(r) mice, the spleens remained small after the virus inoculation. In contrast, Fv(r)/Fv(r) mice receiving Fv(s)/Fv(s) cells responded to the virus with marked spleen enlargement. In the enlarged spleens of the C57BL/6 mice which do not otherwise allow the virus multiplication, a considerable amount of infectious virus was found. The altered response seems to be due to repopulation of destroyed tissues by the transplanted bone marrow cells. It is concluded that the locus Fv is expressed on hemopoietic cells, and cells derived from bone marrow play a predominant role in the development of splenomegaly by Friend leukemia virus.
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PMID:Inheritance of Susceptibility to Friend Mouse Leukemia Virus: VI. Reciprocal Alteration of Innate Resistance or Susceptibility by Bone Marrow Transplantation Between Congenic Strains. 1678 15


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