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Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis

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Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis. / Triviai, Ioanna; Ziegler, Marion; Bergholz, Ulla; Oler, Andrew J; Stübig, Thomas; Prassolov, Vladimir; Fehse, Boris; Kozak, Christine A; Kröger, Nicolaus-Martin; Stocking, Carol.

In: P NATL ACAD SCI USA, Vol. 111, No. 23, 10.06.2014, p. 8595 - 8600.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Triviai, I, Ziegler, M, Bergholz, U, Oler, AJ, Stübig, T, Prassolov, V, Fehse, B, Kozak, CA, Kröger, N-M & Stocking, C 2014, 'Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis', P NATL ACAD SCI USA, vol. 111, no. 23, pp. 8595 - 8600. https://doi.org/10.1073/pnas.1401215111

APA

Triviai, I., Ziegler, M., Bergholz, U., Oler, A. J., Stübig, T., Prassolov, V., Fehse, B., Kozak, C. A., Kröger, N-M., & Stocking, C. (2014). Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis. P NATL ACAD SCI USA, 111(23), 8595 - 8600. https://doi.org/10.1073/pnas.1401215111

Vancouver

Triviai I, Ziegler M, Bergholz U, Oler AJ, Stübig T, Prassolov V et al. Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis. P NATL ACAD SCI USA. 2014 Jun 10;111(23):8595 - 8600. https://doi.org/10.1073/pnas.1401215111

Bibtex

@article{96a6324ff0564f939597f26a538132ad,
title = "Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis",
abstract = "The compound immunodeficiencies in nonobese diabetic (NOD) inbred mice homozygous for the Prkdc(scid) and Il2rg(null) alleles (NSG mice) permit engraftment of a wide-range of primary human cells, enabling sophisticated modeling of human disease. In studies designed to define neoplastic stem cells of primary myelofibrosis (PMF), a myeloproliferative neoplasm characterized by profound disruption of the hematopoietic microenvironment, we observed a high frequency of acute myeloid leukemia (AML) in NSG mice. AML was of mouse origin, confined to PMF-xenografted mice, and contained multiple clonal integrations of ecotropic murine leukemia virus (E-MuLV). Significantly, MuLV replication was not only observed in diseased mice, but also in nontreated NSG controls. Furthermore, in addition to the single ecotropic endogenous retrovirus (eERV) located on chromosome 11 (Emv30) in the NOD genome, multiple de novo germ-line eERV integrations were observed in mice from each of four independent NSG mouse colonies. Analysis confirmed that E-MuLV originated from the Emv30 provirus and that recombination events were not necessary for virus replication or AML induction. Pathogenicity is thus likely attributable to PMF-mediated paracrine stimulation of mouse myeloid cells, which serve as targets for retroviral infection and transformation, as evidenced by integration into the Evi1 locus, a hotspot for retroviral-induced myeloid leukemia. This study thus corroborates a role of paracrine stimulation in PMF disease progression, underlines the importance of target cell type and numbers in MuLV-induced disease, and mandates awareness of replicating MuLV in NOD immunodeficient mice, which can significantly influence experimental results and their interpretation.",
author = "Ioanna Triviai and Marion Ziegler and Ulla Bergholz and Oler, {Andrew J} and Thomas St{\"u}big and Vladimir Prassolov and Boris Fehse and Kozak, {Christine A} and Nicolaus-Martin Kr{\"o}ger and Carol Stocking",
year = "2014",
month = jun,
day = "10",
doi = "10.1073/pnas.1401215111",
language = "English",
volume = "111",
pages = "8595 -- 8600",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "23",

}

RIS

TY - JOUR

T1 - Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis

AU - Triviai, Ioanna

AU - Ziegler, Marion

AU - Bergholz, Ulla

AU - Oler, Andrew J

AU - Stübig, Thomas

AU - Prassolov, Vladimir

AU - Fehse, Boris

AU - Kozak, Christine A

AU - Kröger, Nicolaus-Martin

AU - Stocking, Carol

PY - 2014/6/10

Y1 - 2014/6/10

N2 - The compound immunodeficiencies in nonobese diabetic (NOD) inbred mice homozygous for the Prkdc(scid) and Il2rg(null) alleles (NSG mice) permit engraftment of a wide-range of primary human cells, enabling sophisticated modeling of human disease. In studies designed to define neoplastic stem cells of primary myelofibrosis (PMF), a myeloproliferative neoplasm characterized by profound disruption of the hematopoietic microenvironment, we observed a high frequency of acute myeloid leukemia (AML) in NSG mice. AML was of mouse origin, confined to PMF-xenografted mice, and contained multiple clonal integrations of ecotropic murine leukemia virus (E-MuLV). Significantly, MuLV replication was not only observed in diseased mice, but also in nontreated NSG controls. Furthermore, in addition to the single ecotropic endogenous retrovirus (eERV) located on chromosome 11 (Emv30) in the NOD genome, multiple de novo germ-line eERV integrations were observed in mice from each of four independent NSG mouse colonies. Analysis confirmed that E-MuLV originated from the Emv30 provirus and that recombination events were not necessary for virus replication or AML induction. Pathogenicity is thus likely attributable to PMF-mediated paracrine stimulation of mouse myeloid cells, which serve as targets for retroviral infection and transformation, as evidenced by integration into the Evi1 locus, a hotspot for retroviral-induced myeloid leukemia. This study thus corroborates a role of paracrine stimulation in PMF disease progression, underlines the importance of target cell type and numbers in MuLV-induced disease, and mandates awareness of replicating MuLV in NOD immunodeficient mice, which can significantly influence experimental results and their interpretation.

AB - The compound immunodeficiencies in nonobese diabetic (NOD) inbred mice homozygous for the Prkdc(scid) and Il2rg(null) alleles (NSG mice) permit engraftment of a wide-range of primary human cells, enabling sophisticated modeling of human disease. In studies designed to define neoplastic stem cells of primary myelofibrosis (PMF), a myeloproliferative neoplasm characterized by profound disruption of the hematopoietic microenvironment, we observed a high frequency of acute myeloid leukemia (AML) in NSG mice. AML was of mouse origin, confined to PMF-xenografted mice, and contained multiple clonal integrations of ecotropic murine leukemia virus (E-MuLV). Significantly, MuLV replication was not only observed in diseased mice, but also in nontreated NSG controls. Furthermore, in addition to the single ecotropic endogenous retrovirus (eERV) located on chromosome 11 (Emv30) in the NOD genome, multiple de novo germ-line eERV integrations were observed in mice from each of four independent NSG mouse colonies. Analysis confirmed that E-MuLV originated from the Emv30 provirus and that recombination events were not necessary for virus replication or AML induction. Pathogenicity is thus likely attributable to PMF-mediated paracrine stimulation of mouse myeloid cells, which serve as targets for retroviral infection and transformation, as evidenced by integration into the Evi1 locus, a hotspot for retroviral-induced myeloid leukemia. This study thus corroborates a role of paracrine stimulation in PMF disease progression, underlines the importance of target cell type and numbers in MuLV-induced disease, and mandates awareness of replicating MuLV in NOD immunodeficient mice, which can significantly influence experimental results and their interpretation.

U2 - 10.1073/pnas.1401215111

DO - 10.1073/pnas.1401215111

M3 - SCORING: Journal article

C2 - 24912157

VL - 111

SP - 8595

EP - 8600

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 23

ER -