Prof. Dr. med. Thomas Pabst
Activties and Research Interests
My research group has a long interest in elucidating the transcriptional regulation of normal hematopoiesis as well as the dysregulation of key transcription factors ultimately leading to acute myeloid leukemia (AML). In the center of our interest is the transcription factor CEBPA and its role in the differentiation block of malignant myeloid cells and leukemic stem cells.
We have identified both somatic and germ-line mutations of CEBPA in AML patients, and we have established the prognostic significance of monoallelic and biallelic CEBPA mutations. We found that suppression of CEBPA mRNA is specifically mediated in AML patients with the pathognomonic t(8;21) translocation. Finally, CEBPA translation was identified by our group to be blocked in the presence of inv(16) characteristic for AML patients with the M4Eo subtype.
(1) von Grünigen I, Raschle J, Rüsges-Wolter I, Taleghani BM, Mueller BU, Pabst T. The relapse risk of AML
patients undergoing autologous transplantation correlates with the stem cell mobilizing potential. Leuk Res.
(2) Raschle J, Ratschiller D, Mans S, Mueller BU, Pabst T. High levels of circulating CD34+ cells at autologous
stem cell collection are associated with favourable prognosis in multiple myeloma. Br J Cancer. 105:970-974;
(3) Haefliger S, Klebig C, Schaubitzer K, Schardt J, Timchenko N, Mueller BU, Pabst T. Protein disulfide
isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML. Blood.
(4) Schardt JA, Eyholzer M, Timchenko NA, Mueller BU, Pabst T. The unfolded protein response is activated in
human acute myeloid leukemia and suppresses CEBPA by induction of the RNA-binding protein calreticulin. J
Cell Mol Med. 14:1509-1519; 2010.
(5) Schardt JA, Weber D, Eyholzer M, Mueller BU, Pabst T. Activation of the unfolded protein response is
associated with favorable prognosis in acute myeloid leukemia. Clin Cancer Res 15;3834-3841, 2009.
(6) Pabst T, Eyholzer M, Fos J, Mueller BU. Heterogeneity within AML with CEBPA mutations; only CEBPA
double mutations, but not single CEBPA mutations are associated with favourable prognosis. Brit J Cancer
(7) Pabst T, Eyholzer M, Haefliger S, Schardt J, Mueller BU. Somatic CEBPA mutations are a frequent second
event in families with germline CEBPA mutations and familial acute myeloid leukemia. J Clin Oncol 26;5088-5093,
(8) Helbling D, Mueller BU, Timchenko NA, Eyer M, Betts D, Jotterand M, Meyer-Monard S, Fey MF, Pabst T.
CBFB-SMMHC suppresses the granulocytic differentiation factor CEBPA in acute myeloid leukemia with inv(16)
by activation of Calreticulin. Blood 106:1369-1375, 2005.
(9) Pabst T, Mueller BU, Harakawa N, Schoch C, Haferlach T, Behre G, Hiddemann W, Zhang DE, Tenen DG.
AML1-ETO downregulates the granulocytic differentiation factor C/EBPalpha in t(8;21) myeloid leukemia. Nat
Med 7:444-451, 2001.
(10) Pabst T, Mueller BU, Zhang P, Radomska HS, Narravula S, Schnittger S, Behre G, Hiddemann W, Tenen
DG. Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in
acute myeloid leukemia. Nat Genet 27:263-270, 2001.