Prof. Dr. Robert Slany

Transcriptional priming as global mechanism controlling self renewal and differentiation during hematopoietic development

Institute for Genetics 
Friedrich-Alexander-Universität Erlangen-Nurnberg 
Erwin-Rommel-Str. 3 
91058 Erlangen 

Tel: +49 (0)9131/85 28 527
Fax: +49 (0)9131/85 28 526 



Deutsche Version


Maintaining homeostasis within the hematopoietic system requires a continuous adjustment of the balance between stem-cell self renewal and lineage decisions. Perturbing the underlying control mechanisms can lead to malignant disease. We have shown that the fine tuning of transcriptional elongation at primed or poised promoters is the major transforming mechanism associated with leukemogenic MLL fusion proteins. Complementing our ongoing studies we propose to introduce global run on sequencing methods (GRO-seq) combined with chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) in primary cells to uncover: (I) the promoters governing the transition from stem- towards lineage determined cells (II) the mechanisms of transcriptional regulation that act on these control elements. Furthermore our particular experimental system will allow us to study the response of these master genes towards alterations in transcriptional control mediated by the opposing effects of elongation stimulation versus polycomb mediated repression. This will uncover general and hematopoiesis specific principles how complex organ systems can maintain equilibrium but still stay sufficiently plastic to cope with environmental challenges. In addition it is expected to identify targets for therapeutic intervention of malignant disease.


Group members

... coming soon

Publications within BioSysNet

Maethner E, Garcia-Cuellar MP, Breitinger C, Takacova S, Divoky V, Hess JL, Slany RK (2013). MLL-ENL inhibits polycomb repressive complex 1 to achieve efficient transformation of hematopoietic cells. Cell Rep 3(5):1553-66. 

Publications before BioSysNet

Publications only 2005 and younger, for a full list see:


Takacova S., Slany R., Bartkova J., Stranecky V., Dolezel P., Luzna P., Bartek J., Divoky V. (2012) DNA Damage Response and Inflammatory Signaling Limit the MLL-ENL induced Leukemogenesis in vivo, CancerCell, in press


Monroe S.C., Joa S.Y., Sandersa D.S., Basrura V., Elenitoba-Johnsona K.S., Slany R.K., and Hess J.L. (2011) MLL-AF9 alters the dynamic association of transcriptional regulators with leukemogenic target genes, Exp.Hematol, 39:77-86


Wildenhain S., Ruckert C., Röttgers S., Harbott J., Ludwig W.D., Schuster F.R., Beldjord K., Binder V., Slany R., Hauer J., and Borkhardt A. (2010) Expression of cell-cell interacting genes distinguishes HLXB9/TEL from MLL-positive childhood acute myeloid leukemia. Leukemia, Sep;24(9):1657-1660


Slany R.K. (2010) When speed matters: Leukemogenic transformation by MLL fusion proteins. Cell Cycle, 9(13)


Bach C., Buhl S., Mueller D., García-Cuéllar M.P., Maethner E., and Slany R.K. (2010) Leukemogenic transformation by HOXA-cluster genes, Blood, 115:2910-18


Röttgers S., Gombert M., Teigler-Schlegel A., Busch K., Gamerdinger U., Slany R., Harbott J., and Borkhardt A. (2010) ALK fusion genes in children with “atypical juvenile myelomonocytic leukemia”, Leukemia, 24:1197-2000


Müller D., Garcia-Cuellar M.P., Bach C., Buhl S., Mäthner E., and Slany R.K. (2009) Misguided Transcriptional Elongation Causes Mixed Lineage Leukemia, PLOS Biology, 7(11):e1000249 [chosen as research highlight in Nature Genetics 42, 19 (2010)]


Röhrs S., Dirks W.G., Meyer C., Marschalek R., Scherr M., Slany R., Wallace A., Drexler H.G. and Quentmeier H. (2009) Hypomethylation and expression of BEX2, IGSF4 and TIMP3 indicative of MLL translocations in Acute Myeloid Leukemia, Molecular Cancer, 16; 8:86


Bach C., and Slany R.K. (2009) Molecular pathology of mixed-lineage-leukemia, Future Oncology, 5, 1271-1281


Meyer M., Rübsamen D., Slany R.K., Illmer T., Stabla K., Roth P., Stiewe T., Eilers M., and Neubauer A. (2009) Oncogenic RAS Enables DNA Damage- and p53-Dependent Differentiation of Acute Myeloid Leukemia Cells in Response to Chemotherapy, PLOS One; 4: e7768


Schwieger M., Schüler A, Forster M., Engelmann A., Arnold M.A., Delwel R., Valk P.J., Löhler J., Slany R.K., Olson E.N., and Stocking C. (2009) Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C, Blood, 114:2476-88


Slany R.K. (2009) The molecular biology of mixed lineage leukemia, Hematologica, 94:984-993


Garcia-Cuellar M.P., Mederer D., and Slany R.K. (2009) Identification of protein interaction partners by the yeast two hybrid system, Methods Mol Biol, 538:1-21 (book chapter)


Bach C., Mueller D., Buhl S., Garcia-Cuellar M.P., and Slany R.K (2009) Alterations of the CxxC domain preclude oncogenic activation of Mixed Lineage Leukemia 2, Oncogene, 28: 815-823. Epub 2008 Dec 8.


Müller D., Bach C., Zeisig D., Garcia-Cuellar M.P., Monroe S., Sreekumar A., Zhou R., Nesvizhskii A., Chinnaiyan A., Hess J.L., and Slany R.K. (2007) A Role for the MLL Fusion Partner ENL in Transcriptional Elongation and Chromatin Modification, Blood, 110: 4445-4454


Caslini C., Yang Z., El-Osta M., Milne T.A., Slany R.K., and Hess J.L. (2007) Interaction of MLL Amino Terminal Sequences with Menin Is Required for Transformation, Cancer Res ,67 7275-7283


Eguchi M, Eguchi-Ishimae M, Knight D, Kearney L, Slany R, Greaves M (2006) MLL chimeric protein activation renders cells vulnerable to chromosomal damage: An explanation for the very short latency of infant leukemia, Genes Chromosomes Cancer, 45(8),754-60


Pession A, Lo Nigro L, Montemurro L, Serravalle S, Fazzina R, Izzi G, Nucifora G, Slany R, Tonelli R. (2006) ArgBP2, encoding a negative regulator of ABL, is fused to MLL in a case of infant M5 acute myeloid leukemia involving 4q35 and 11q23, Leukemia, 20(7), 1310-1313


Hess J.L., Bittner C.B., Zeisig D.T., Bach C., Fuchs U., Borkhardt A., Frampton J., and Slany R.K. (2006) c-Myb is an essential downstream target for homeobox mediated transformation of hematopoietic cells, Blood, 108(1), 297-304


Milne T.A., Martin M.E., Brock H.W., Slany R.K., and Hess J.L. (2005) Leukemogenic MLL fusion proteins bind across a broad region of the Hox a9 locus and promote gene activation and multiple histone modifications, Cancer Res, 65(24), 11367-11374


Slany R.K. (2005) Chromatin control of gene expression: Mixed lineage leukemia protein SETs the stage for transcription. Commentary, Proc. Natl. Acad. Sci, 102(41), 14481-14482


Slany R.K. (2005) When epigenetics kills: MLL fusion proteins in leukemia. Review Hematol Oncol., 23(1), 1-9


Zeisig D.T., Bittner C.B., Zeisig B.B., Garcia-Cuellar M.P., Hess J.L., and Slany R.K. (2005) The eleven-nineteen-leukemia protein ENL connects nuclear MLL fusion partners with chromatin, Oncogene, 24(35), 5525-5532