Systematics of RNA Tumor Viruses and Virus-Like Particles of Human Origin

Miller, N. R.; Saxinger, W. C.; Reitz, M. S.; Gallagher, Robert E.; Wu, A. M.; Gallo, Robert C.; Gillespie, David

doi:10.1073/pnas.71.8.3177

Cited by 35 publications

(9 citation statements)

References 14 publications

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“…With human acute myelogenous leukemia cells, this polymerase was shown by immuno-350 logical studies to be specifically related to reverse transcriptase from the two known oncogenic primate type C viruses, the woolly monkey (simian) sarcoma virus (SiSV) and the gibbon ape leukemia virus (GALV) (11)(12)(13)(14). Also, nucleic acids associated with the reverse transcriptase have some nucleotide sequences that are similar to those of some RNA tumor viruses (14)(15)(16)(17). Finally, fresh blood leukocytes from five cases of acute myelogenous leukemia tested were recently determined to contain a protein strongly related to group specific antigen (p30 protein) from SiSV (18).…”

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Type C RNA Tumor Virus Isolated from Cultured Human Acute Myelogenous Leukemia Cells

Gallagher

Gallo

1975

Science

205

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Previously, type C RNA tumor virus-related components have been described in blood leukocytes from patients with acute myelogenous leukemia. These components, for example, reverse transcriptase, have been shown to be most closely related to those from two oncogenic subhuman primate type C viruses (woolly monkey sarcoma virus and gibbon ape leukemia virus). Now, we report the continuous production of budding type C viruses with the same characteristic reverse transcriptase by three separate culturings of leukocytes from a single bleeding from a patient with acute myelogenous leukemia. These isolations were made possible by the discovery of a source of conditioned media which sustains exponential growth of human myelogenous leukemia cells in liquid suspension culture.

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Type C RNA Tumor Virus Isolated from Cultured Human Acute Myelogenous Leukemia Cells

Gallagher

Gallo

1975

Science

205

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“…Molecular hybridization is yet needed to show that, indeed, these particles from preleukemic patients contain leukemogenic information as has been demonstrated in similar particles from leukemic patients (6,7). Should this be true, diagnosis and treatment in the preleukemic phase of the disease may be feasible.…”

Section: Resultsmentioning

confidence: 99%

Oncornavirus-like particles from cultured bone marrow cells preceding leukemia and malignant histiocytosis.

Vosika¹,

Krivit²,

Gerrard³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

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ABSTRACr Particles with the density and enzymatic activity characteristic of known oncornavirus have been previously described' in bone marrow cells from patients with leukemia in relapse and in remission. We have confirmed these findings and studied two patients in whom preleukemia was among the diagnostic considerations. Following cultivation of bone marrow from these patients for 1 week in conditioned media with dexamethasone, a high-speed pellet of the supernatant fluid and disrupted cells was prepared and analyzed on a sucrose gradient for enzymatic activity characteristic of RNA-directed DNA polymerase (reverse transcriptase). Peaks of endogenous DNA polymerase activity showing ribonuclease sensitivity and/or stimulation with the synthetic template poly(rC)dG~hs218 were demonstrated in both patients at densities of 1.15 to 1.19 and 1.21 to 1.24 g/ml. Subsequently diagnosis 2 and 4 months after initial evaluation 'revealed acute myelogenous leukemia and malignant histiocytosis, respectively. Prior studies have suggested a possible etiological significance of such particles in human leukemia. The demonstration of similar particles preceding clinically overt disease in these patients supports this hypothesis and offers the possibility of early diagnosis and treatment.A cytoplasmic particle with the density, high-molecularweight RNA, and RNA-dependent DNA polymerase characteristic of known RNA tumor viruses has been demonstrated in malignant cells from patients with leukemia (1-3). Following cultivation with conditioned media, Mak et al. have demonstrated an increase and release of such particles from cells of leukemic patients both in relapse and in firm hematological remission with no evidence of disease (3, 4). Molecular hybridization (5-7) and immunological studies (8,9) have added significance to these particles by demonstrating a close relationship between them and known oncogenic agents of primate origin, confirming earlier reports of homology between nucleic acid of human leukemia cells and murine leukemia virus (10,11).We now report studies of two patients in whom, on the basis of history and clinical and laboratory examination, the possibility of preleukemia was considered as part of the differential diagnosis. Extensive investigation of both patients failed to reveal any definite histological evidence to support the diagnosis of leukemia. Bone marrow obtained at that time from both patients showed clear biochemical evidence of oncornavirus-like particles 2 and 4 months prior to the diagnosis of acute myelogenous leukemia and malignant histiocytosis, respectively. MATERIALS AND METHODS Patient Material. Bone marrow from these two patients and from patients with either acute myelogenous leukemia (AML) or chromic myelogenous leukemia (CML) was obtained by aspiration from the posterior iliac crest. Peripheral blood was used in cases with high peripheral blast counts. Normal bone marrow was obtained from three normal marrow donors in the course of bone marrow transplantation.Method of Cultivation. Bone m...

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“…This includes evidence in some patients with leukemia and preleukemia of a polymerase related to reverse transcriptase of these viruses (5,6,8,14,41), a protein antigenically related to the virus p30 structural protein (7,(21)(22)(23), and some cytoplasmic nucleic acid sequences (11)(12)(13)(14). There are also some reports of isolation of replicating leukemic blood or bone marrow cells.…”

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“…Data are accumulating that indicate the presence of type-Ctumor-virus-like components in some human tissues . Cytoplasmic nucleic acids with sequences related to the RNA of Rauscher murine leukemia virus (MuLVR) and other viruses have been described (4,(9)(10)(11)(12)(13)(14)(15)(16)(17). Recently, nucleic acids and proteins related to the two known primate type-C virus groups-the simian sarcoma virus/gibbon ape leukemia virus group and the baboon endogenous virus group-have been reported in fresh human tissues (5-8, 11-14, 16, 18-23) (20)(21)(22)(23) have been contested (24).…”

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Rauscher-leukemia-virus-related sequences in human DNA: presence in some tissues of some patients with hemotopoietic neoplasias and absence in DNA from other tissues.

Aulakh¹,

Gallo²

1977

Proc. Natl. Acad. Sci. U.S.A.

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Nature 262,[190][191][192][193][194][195], because there is no sequence homology between nucleic acids from MuLVR and baboon virus. The absence of these nucleic acid sequences in many tissues of patients with neoplasia and from the few tissues examined from people with nonneoplastic disease suggests that they are not endogenous elements but are acquired after fertilization. Taken together with the previous detection of baboon and woolly monkey type-C viral related components in some human tumors, the results suggest acquisition of at least three types of type-C viral sequences in the human population. Data are accumulating that indicate the presence of type-Ctumor-virus-like components in some human tissues (1-23). Cytoplasmic nucleic acids with sequences related to the RNA of Rauscher murine leukemia virus (MuLVR) and other viruses have been described (4, 9-17). Recently, nucleic acids and proteins related to the two known primate type-C virus groups-the simian sarcoma virus/gibbon ape leukemia virus group and the baboon endogenous virus group-have been reported in fresh human tissues (5-8, 11-14, 16, 18-23) The objective of experiments reported here was to examine DNA from human tissues for sequences related to RNA of MuLVR in more detail and with more carefully prepared cDNA probes. We report: (i) detection of nucleic acid sequences distantly related to MuLVR in DNA from spleens of some patients with acute myelogenous leukemia (AML), Hodgkin's disease, and multiple myeloma; (ii) absence of these sequences in DNA from apparently uninvolved tissues of the same patients with neoplasia and from the normal human tissues tested. Since MuLVR and the baboon endogenous virus are not detectably related (32), the detection of MuLVR-related DNA sequences is not explained by the previously reported presence of proviral sequences of baboon virus in DNA from some leukemia patients. Taken together, the results show at least two independent sets of oncornavirus-related sequences in the DNA from some leukemia patients. While the mode, source, and time of acquisition, and relevance to etiology, must be speculative, interspecies transmission of one or both agents may be involved.MATERIALS AND METHODS Purification of DNA from Human Tissues. The tissues used in these experiments were uncultured specimens obtained at the time of autopsy and kept frozen at -80°until the isolation of DNA. The organ tissues obtained from people with neoplasia were infiltrated with tumor cells. The tissues were lysed in a

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Systematics of RNA Tumor Viruses and Virus-Like Particles of Human Origin

Cited by 35 publications

References 14 publications

Type C RNA Tumor Virus Isolated from Cultured Human Acute Myelogenous Leukemia Cells

Type C RNA Tumor Virus Isolated from Cultured Human Acute Myelogenous Leukemia Cells

Oncornavirus-like particles from cultured bone marrow cells preceding leukemia and malignant histiocytosis.

Rauscher-leukemia-virus-related sequences in human DNA: presence in some tissues of some patients with hemotopoietic neoplasias and absence in DNA from other tissues.

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