My Research

Ruud Delwel started his career in 1983 in the lab of Bob Lowenberg, studying the in vitro behaviour of human acute myeloid leukemia cells in vitro. He obtained his PhD in 1990 (Cum Laude) and became a post doctoral fellow in the group of Dr. James Ihly, at the St. Jude’s Children’s Research Hospital in Memphis, Tennessee Leiden, and carried out retroviral insertional mutagenesis to discover novel disease genes in AML. He discovered the EVI1 gene to be one of the most severe disease genes in mouse leukemia’s and in human. When back in the Netherlands, ErasmusMC, he moved on studying the biological consequences of altered gene expression in human and murine AML.

His two major breakthrough studies are 1) The discovery that human AML can be classified based on unique gene expression signatures and on specific gene methylation profiles. These studies led to the uncover of a subset of unique AML cases with aberrant expression of the EVI1 gene. Further in depth analysis revealed a unique mechanism of enhancer deregulation in a subset of human EVI1-AMLs. Ruud Delwel and his team have been able to combine patient analysis with molecular studies using in vitro and in vivo modelling to improve our insight into molecular aspects of acute myeloid leukemia. These studies and the proposal that followed on these studies have been awarded by the Dutch Cancer Society or "Koningin Wilhelmina Fonds” with the "Koningin Wilhelmina Onderzoek prijs", or KWO Award.

Our research now focusses on the mechanisms of aberrant gene (EVI1) control by hijacked enhancers and how we may interfere with the aberrant expression of those genes. Applying sophisticated in vitro models we screened for compounds, using the drug repurposing library obtained by Oncode, to uncover ways to interfere with oncogene expression. We obtained several interesting hits, which are investigated further in the next five years within Oncode.

Awards

• 2017: Jose Carreras Lecture/Price
• 2015: KWO Award
• 1994: Fellowship from the Royal Dutch Academy of Science (KNAW)

Key publications

1. Smeenk L, Ottema S, Mulet-Lazaro R, Ebert A, Havermans M, Varea AA, Fellner M, Pastoors D, van Herk S, Erpelinck-Verschueren C, Grob T, Hoogenboezem RM, Kavelaars FG, Matson DR, Bresnick EH, Bindels EM, Kentsis A, Zuber J, Ruud Delwel. Selective Requirement of MYB for Oncogenic Hyperactivation of a Translocated Enhancer in Leukemia. Cancer Discov. 2021 Nov;11(11):2868-2883.
2. Ottema S, Mulet-Lazaro R, Erpelinck-Verschueren C, van Herk S, Havermans M, Arricibita Varea A, Vermeulen M, Beverloo HB, Gröschel S, Haferlach T, Haferlach C, J Wouters B, Bindels E, Smeenk L, Ruud Delwel. The leukemic oncogene EVI1 hijacks a MYC super-enhancer by CTCF-facilitated loops. Nat Commun. 2021 Sep 28;12(1):5679.
3. Mulet-Lazaro R, van Herk S, Erpelinck C, Bindels E, Sanders MA, Vermeulen C, Renkens I, Valk P, Melnick AM, de Ridder J, Rehli M, Gebhard C, Ruud Delwel, Wouters BJ. Allele-specific expression of GATA2 due to epigenetic dysregulation in CEBPA double-mutant AML. Blood. 2021 Jul 15;138(2):160-177
4. Sophie Ottema, Roger Mulet-Lazaro, H. Berna Beverloo, Claudia Erpelinc, Stanley van Herk, Marije Havermans, Tim Grob, Peter J. M. Valk, Eric Bindels, Torsten Haferlach, Claudia Haferlach, Leonie Smeenk, Ruud Delwel. Atypical 3q26/MECOM rearrangements genocopy inv(3)/t(3;3) in acute myeloid leukemia. Blood. 2020 Jul 9;136(2):224-234.
5. Gröschel, S., Sanders, M.A., Hoogenboezem, R., De Wit, E., Bouwman, B.A.M., Erpelinck, C., ... & Ruud Delwel. (2014). An oncogenic enhancer-rearrangement causes concomitant deregulation of EVI1 and GATA2 in leukemia. 2014, Cell, 157(2), 369-81.