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A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2

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A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2. / Kaufmann, Kai B; Gründer, Albert; Hadlich, Tobias; Wehrle, Julius; Gothwal, Monika; Bogeska, Ruzhica; Seeger, Thalia S; Kayser, Sarah; Pham, Kien-Binh; Jutzi, Jonas S; Ganzenmüller, Lucas; Steinemann, Doris; Schlegelberger, Brigitte; Wagner, Julia M; Jung, Manfred; Will, Britta; Steidl, Ulrich; Aumann, Konrad; Werner, Martin; Günther, Thomas; Schüle, Roland; Rambaldi, Alessandro; Pahl, Heike L.

In: J EXP MED, Vol. 209, No. 1, 16.01.2012, p. 35-50.

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

Harvard

Kaufmann, KB, Gründer, A, Hadlich, T, Wehrle, J, Gothwal, M, Bogeska, R, Seeger, TS, Kayser, S, Pham, K-B, Jutzi, JS, Ganzenmüller, L, Steinemann, D, Schlegelberger, B, Wagner, JM, Jung, M, Will, B, Steidl, U, Aumann, K, Werner, M, Günther, T, Schüle, R, Rambaldi, A & Pahl, HL 2012, 'A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2', J EXP MED, vol. 209, no. 1, pp. 35-50. https://doi.org/10.1084/jem.20110540

APA

Kaufmann, K. B., Gründer, A., Hadlich, T., Wehrle, J., Gothwal, M., Bogeska, R., Seeger, T. S., Kayser, S., Pham, K-B., Jutzi, J. S., Ganzenmüller, L., Steinemann, D., Schlegelberger, B., Wagner, J. M., Jung, M., Will, B., Steidl, U., Aumann, K., Werner, M., ... Pahl, H. L. (2012). A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2. J EXP MED, 209(1), 35-50. https://doi.org/10.1084/jem.20110540

Vancouver

Kaufmann KB, Gründer A, Hadlich T, Wehrle J, Gothwal M, Bogeska R et al. A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2. J EXP MED. 2012 Jan 16;209(1):35-50. https://doi.org/10.1084/jem.20110540

Bibtex

@article{c523d7bfe479457f9daf1ba2d95e3654,
title = "A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2",
abstract = "The molecular pathophysiology of myeloproliferative neoplasms (MPNs) remains poorly understood. Based on the observation that the transcription factor NF-E2 is often overexpressed in MPN patients, independent of the presence of other molecular aberrations, we generated mice expressing an NF-E2 transgene in hematopoietic cells. These mice exhibit many features of MPNs, including thrombocytosis, leukocytosis, Epo-independent colony formation, characteristic bone marrow histology, expansion of stem and progenitor compartments, and spontaneous transformation to acute myeloid leukemia. The MPN phenotype is transplantable to secondary recipient mice. NF-E2 can alter histone modifications, and NF-E2 transgenic mice show hypoacetylation of histone H3. Treatment of mice with the histone deacetylase inhibitor (HDAC-I) vorinostat restored physiological levels of histone H3 acetylation, decreased NF-E2 expression, and normalized platelet numbers. Similarly, MPN patients treated with an HDAC-I exhibited a decrease in NF-E2 expression. These data establish a role for NF-E2 in the pathophysiology of MPNs and provide a molecular rationale for investigating epigenetic alterations as novel targets for rationally designed MPN therapies.",
keywords = "Animals, Blood Cell Count, Blood Cells, Cell Differentiation, Chromatin, Disease Models, Animal, Disease Progression, Gene Expression, Gene Expression Regulation, Hematopoietic Stem Cells, Histone Deacetylase Inhibitors, Humans, Leukemia, Mice, Mice, Transgenic, Myeloproliferative Disorders, NF-E2 Transcription Factor, Phenotype",
author = "Kaufmann, {Kai B} and Albert Gr{\"u}nder and Tobias Hadlich and Julius Wehrle and Monika Gothwal and Ruzhica Bogeska and Seeger, {Thalia S} and Sarah Kayser and Kien-Binh Pham and Jutzi, {Jonas S} and Lucas Ganzenm{\"u}ller and Doris Steinemann and Brigitte Schlegelberger and Wagner, {Julia M} and Manfred Jung and Britta Will and Ulrich Steidl and Konrad Aumann and Martin Werner and Thomas G{\"u}nther and Roland Sch{\"u}le and Alessandro Rambaldi and Pahl, {Heike L}",
year = "2012",
month = jan,
day = "16",
doi = "10.1084/jem.20110540",
language = "English",
volume = "209",
pages = "35--50",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "1",

}

RIS

TY - JOUR

T1 - A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2

AU - Kaufmann, Kai B

AU - Gründer, Albert

AU - Hadlich, Tobias

AU - Wehrle, Julius

AU - Gothwal, Monika

AU - Bogeska, Ruzhica

AU - Seeger, Thalia S

AU - Kayser, Sarah

AU - Pham, Kien-Binh

AU - Jutzi, Jonas S

AU - Ganzenmüller, Lucas

AU - Steinemann, Doris

AU - Schlegelberger, Brigitte

AU - Wagner, Julia M

AU - Jung, Manfred

AU - Will, Britta

AU - Steidl, Ulrich

AU - Aumann, Konrad

AU - Werner, Martin

AU - Günther, Thomas

AU - Schüle, Roland

AU - Rambaldi, Alessandro

AU - Pahl, Heike L

PY - 2012/1/16

Y1 - 2012/1/16

N2 - The molecular pathophysiology of myeloproliferative neoplasms (MPNs) remains poorly understood. Based on the observation that the transcription factor NF-E2 is often overexpressed in MPN patients, independent of the presence of other molecular aberrations, we generated mice expressing an NF-E2 transgene in hematopoietic cells. These mice exhibit many features of MPNs, including thrombocytosis, leukocytosis, Epo-independent colony formation, characteristic bone marrow histology, expansion of stem and progenitor compartments, and spontaneous transformation to acute myeloid leukemia. The MPN phenotype is transplantable to secondary recipient mice. NF-E2 can alter histone modifications, and NF-E2 transgenic mice show hypoacetylation of histone H3. Treatment of mice with the histone deacetylase inhibitor (HDAC-I) vorinostat restored physiological levels of histone H3 acetylation, decreased NF-E2 expression, and normalized platelet numbers. Similarly, MPN patients treated with an HDAC-I exhibited a decrease in NF-E2 expression. These data establish a role for NF-E2 in the pathophysiology of MPNs and provide a molecular rationale for investigating epigenetic alterations as novel targets for rationally designed MPN therapies.

AB - The molecular pathophysiology of myeloproliferative neoplasms (MPNs) remains poorly understood. Based on the observation that the transcription factor NF-E2 is often overexpressed in MPN patients, independent of the presence of other molecular aberrations, we generated mice expressing an NF-E2 transgene in hematopoietic cells. These mice exhibit many features of MPNs, including thrombocytosis, leukocytosis, Epo-independent colony formation, characteristic bone marrow histology, expansion of stem and progenitor compartments, and spontaneous transformation to acute myeloid leukemia. The MPN phenotype is transplantable to secondary recipient mice. NF-E2 can alter histone modifications, and NF-E2 transgenic mice show hypoacetylation of histone H3. Treatment of mice with the histone deacetylase inhibitor (HDAC-I) vorinostat restored physiological levels of histone H3 acetylation, decreased NF-E2 expression, and normalized platelet numbers. Similarly, MPN patients treated with an HDAC-I exhibited a decrease in NF-E2 expression. These data establish a role for NF-E2 in the pathophysiology of MPNs and provide a molecular rationale for investigating epigenetic alterations as novel targets for rationally designed MPN therapies.

KW - Animals

KW - Blood Cell Count

KW - Blood Cells

KW - Cell Differentiation

KW - Chromatin

KW - Disease Models, Animal

KW - Disease Progression

KW - Gene Expression

KW - Gene Expression Regulation

KW - Hematopoietic Stem Cells

KW - Histone Deacetylase Inhibitors

KW - Humans

KW - Leukemia

KW - Mice

KW - Mice, Transgenic

KW - Myeloproliferative Disorders

KW - NF-E2 Transcription Factor

KW - Phenotype

U2 - 10.1084/jem.20110540

DO - 10.1084/jem.20110540

M3 - SCORING: Journal article

C2 - 22231305

VL - 209

SP - 35

EP - 50

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 1

ER -