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  • Z01
    • Backofen
    • Manke
  • Z02
    • Breit
    • Einsle
    • Günther
  • Z03 Central tasks

B02 Epigenetic effects of transcription factor NF-E2 in myeloproliferative neoplasms

Heike Pahl

Heike Pahl

Principal investigator of

Myeloproliferative Neoplasms (MPNs) constitute haematologic malignancies for which no curative targeted therapies are available. Epigenetic alterations and elevated activity of the transcription factor NFE2 contribute significantly to the pathophysiology of MPNs. We have identified several epigenetic regulators as novel NFE2 target genes. To generate better tools for the identification of targeted therapies we established two novel MPN mouse models. The long-term goals of this project are to demonstrate the pre-clinical efficacy of epigenetic therapy in MPN models and to translate these results into novel therapies for patients with MPN.

Selected project-relevant publications

  • Peeken J.C., Jutzi J.S., Wehrle J., Koellerer C., Staehle H.F., Becker H., Schoenwandt E., Seeger T.S., Schanne D.H., Gothwal M., Ott C.J., Grunder A. and Pahl H.L. (2018) Epigenetic regulation of NFE2 overexpression in myeloproliferative neoplasms. Blood 131, 2065-2073.
  • Gothwal M., Wehrle J., Aumann K., Zimmermann V., Grunder A. and Pahl H.L. (2016) A novel role for nuclear factor-erythroid 2 in erythroid maturation by modulation of mitochondrial autophagy. Haematologica 101, 1054-1064.
  • Aumann K., Werner M. and Pahl H.L. (2016) Immunohistochemical staining of transcription factor NFE2 for the discrimination of primary myelofibrosis from essential thrombocythemia. Hum Pathol 53, 195-196.
  • Jutzi J.S. and Pahl H.L. (2015) The Hen or the Egg: Inflammatory Aspects of Murine MPN Models. Mediators Inflamm 2015, 101987.
  • Gajer J.M., Furdas S.D., Grunder A., Gothwal M., Heinicke U., Keller K., Colland F., Fulda S., Pahl H.L., Fichtner I., Sippl W. and Jung M. (2015) Histone acetyltransferase inhibitors block neuroblastoma cell growth in vivo. Oncogenesis 4, e137.
  • Rheinemann L., Seeger T.S., Wehrle J. and Pahl H.L. (2014) NFE2 regulates transcription of multiple enzymes in the heme biosynthesis pathway. Haematologica 99, e208-210.
  • Jutzi J.S., Bogeska R., Nikoloski G., Schmid C.A., Seeger T.S., Stegelmann F., Schwemmers S., Grunder A., Peeken J.C., Gothwal M., Wehrle J., Aumann K., Hamdi K., Dierks C., Kamar Wang W., Dohner K., Jansen J.H. and Pahl H.L. (2013) MPN patients harbor recurrent truncating mutations in transcription factor NF-E2. J Exp Med 210, 1003-1019.
  • Bogeska R. and Pahl H.L. (2013) Elevated nuclear factor erythroid-2 levels promote epo-independent erythroid maturation and recapitulate the hematopoietic stem cell and common myeloid progenitor expansion observed in polycythemia vera patients. Stem Cells Transl Med 2, 112-117.
  • Aumann K., Frey A.V., May A.M., Hauschke D., Kreutz C., Marx J.P., Timmer J., Werner M. and Pahl H.L. (2013) Subcellular mislocalization of the transcription factor NF-E2 in erythroid cells discriminates prefibrotic primary myelofibrosis from essential thrombocythemia. Blood 122, 93-99.
  • Kaufmann K.B., Grunder A., Hadlich T., Wehrle J., Gothwal M., Bogeska R., Seeger T.S., Kayser S., Pham K.B., Jutzi J.S., Ganzenmuller L., Steinemann D., Schlegelberger B., Wagner J.M., Jung M., Will B., Steidl U., Aumann K., Werner M., Gunther T., Schule R., Rambaldi A. and Pahl H.L. (2012) A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2. J Exp Med 209, 35-50.