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Enhanced expression of the sphingosine-1-phosphate-receptor-3 causes acute myelogenous leukemia in mice

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Enhanced expression of the sphingosine-1-phosphate-receptor-3 causes acute myelogenous leukemia in mice. / Vorbach, Samuel; Gründer, Albert; Zhou, Fengbiao; Koellerer, Christoph; Jutzi, Jonas S; Simoni, Manuela; Riccetti, Laura; Valk, Peter J; Sanders, Mathijs A; Müller-Tidow, Carsten; Nofer, Jerzy-Roch; Pahl, Heike L; Potì, Francesco.

In: LEUKEMIA, Vol. 34, No. 3, 03.2020, p. 721-734.

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

Harvard

Vorbach, S, Gründer, A, Zhou, F, Koellerer, C, Jutzi, JS, Simoni, M, Riccetti, L, Valk, PJ, Sanders, MA, Müller-Tidow, C, Nofer, J-R, Pahl, HL & Potì, F 2020, 'Enhanced expression of the sphingosine-1-phosphate-receptor-3 causes acute myelogenous leukemia in mice', LEUKEMIA, vol. 34, no. 3, pp. 721-734. https://doi.org/10.1038/s41375-019-0577-7

APA

Vorbach, S., Gründer, A., Zhou, F., Koellerer, C., Jutzi, J. S., Simoni, M., Riccetti, L., Valk, P. J., Sanders, M. A., Müller-Tidow, C., Nofer, J-R., Pahl, H. L., & Potì, F. (2020). Enhanced expression of the sphingosine-1-phosphate-receptor-3 causes acute myelogenous leukemia in mice. LEUKEMIA, 34(3), 721-734. https://doi.org/10.1038/s41375-019-0577-7

Vancouver

Vorbach S, Gründer A, Zhou F, Koellerer C, Jutzi JS, Simoni M et al. Enhanced expression of the sphingosine-1-phosphate-receptor-3 causes acute myelogenous leukemia in mice. LEUKEMIA. 2020 Mar;34(3):721-734. https://doi.org/10.1038/s41375-019-0577-7

Bibtex

@article{b93d78060d8c4bdc821abd6800d90e87,
title = "Enhanced expression of the sphingosine-1-phosphate-receptor-3 causes acute myelogenous leukemia in mice",
abstract = "Acute myeloid leukemia (AML) carries a 10-100 fold lower mutational burden than other neoplastic entities. Mechanistic explanations for why a low number of mutations suffice to induce leukemogenesis are therefore required. Here we demonstrate that transgenic overexpression of the wild type sphingosine-1-phosphate receptor 3 (S1P3) in murine hematopoietic stem cells is sufficient to induce a transplantable myeloid leukemia. In contrast, S1P3 expression in more mature compartments does not cause malignant transformation. Treatment with the sphingosine phosphate receptor modulator Fingolimod, which prevents receptor signaling, normalized peripheral blood cell counts and reduced spleen sizes in S1P3 expressing mice. Gene expression analyses in AML patients revealed elevated S1P3 expression specifically in two molecular subclasses. Our data suggest a previously unrecognized contribution of wild type S1P3 signaling to leukemogenesis that warrants the exploration of S1P3 antagonists in preclinical AML models.",
author = "Samuel Vorbach and Albert Gr{\"u}nder and Fengbiao Zhou and Christoph Koellerer and Jutzi, {Jonas S} and Manuela Simoni and Laura Riccetti and Valk, {Peter J} and Sanders, {Mathijs A} and Carsten M{\"u}ller-Tidow and Jerzy-Roch Nofer and Pahl, {Heike L} and Francesco Pot{\`i}",
year = "2020",
month = mar,
doi = "10.1038/s41375-019-0577-7",
language = "English",
volume = "34",
pages = "721--734",
journal = "LEUKEMIA",
issn = "0887-6924",
publisher = "NATURE PUBLISHING GROUP",
number = "3",

}

RIS

TY - JOUR

T1 - Enhanced expression of the sphingosine-1-phosphate-receptor-3 causes acute myelogenous leukemia in mice

AU - Vorbach, Samuel

AU - Gründer, Albert

AU - Zhou, Fengbiao

AU - Koellerer, Christoph

AU - Jutzi, Jonas S

AU - Simoni, Manuela

AU - Riccetti, Laura

AU - Valk, Peter J

AU - Sanders, Mathijs A

AU - Müller-Tidow, Carsten

AU - Nofer, Jerzy-Roch

AU - Pahl, Heike L

AU - Potì, Francesco

PY - 2020/3

Y1 - 2020/3

N2 - Acute myeloid leukemia (AML) carries a 10-100 fold lower mutational burden than other neoplastic entities. Mechanistic explanations for why a low number of mutations suffice to induce leukemogenesis are therefore required. Here we demonstrate that transgenic overexpression of the wild type sphingosine-1-phosphate receptor 3 (S1P3) in murine hematopoietic stem cells is sufficient to induce a transplantable myeloid leukemia. In contrast, S1P3 expression in more mature compartments does not cause malignant transformation. Treatment with the sphingosine phosphate receptor modulator Fingolimod, which prevents receptor signaling, normalized peripheral blood cell counts and reduced spleen sizes in S1P3 expressing mice. Gene expression analyses in AML patients revealed elevated S1P3 expression specifically in two molecular subclasses. Our data suggest a previously unrecognized contribution of wild type S1P3 signaling to leukemogenesis that warrants the exploration of S1P3 antagonists in preclinical AML models.

AB - Acute myeloid leukemia (AML) carries a 10-100 fold lower mutational burden than other neoplastic entities. Mechanistic explanations for why a low number of mutations suffice to induce leukemogenesis are therefore required. Here we demonstrate that transgenic overexpression of the wild type sphingosine-1-phosphate receptor 3 (S1P3) in murine hematopoietic stem cells is sufficient to induce a transplantable myeloid leukemia. In contrast, S1P3 expression in more mature compartments does not cause malignant transformation. Treatment with the sphingosine phosphate receptor modulator Fingolimod, which prevents receptor signaling, normalized peripheral blood cell counts and reduced spleen sizes in S1P3 expressing mice. Gene expression analyses in AML patients revealed elevated S1P3 expression specifically in two molecular subclasses. Our data suggest a previously unrecognized contribution of wild type S1P3 signaling to leukemogenesis that warrants the exploration of S1P3 antagonists in preclinical AML models.

U2 - 10.1038/s41375-019-0577-7

DO - 10.1038/s41375-019-0577-7

M3 - SCORING: Journal article

C2 - 31636343

VL - 34

SP - 721

EP - 734

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

IS - 3

ER -