Group leader: Dr. Ronald Stam
As the 5-year event free survival chances for patients diagnosed with MLL-rearranged acute lymphoblastic and myeloid leukemia, or NUP98-rearranged acute myeloid leukemia, still remain <40%, current therapeutic regimens clearly are not suitable for these specific patient groups, emphasizing the urgent need for more adequate treatment options for these children. Using various high-throughput screening approaches such as elaborate drug library screens, RNA and whole genome sequencing, CRISPR/Cas9 library screens, single-cell sequencing, microarray analyses, and protein array assays, we are continuously searching for novel therapeutic targets and innovative treatment strategies. Subsequently, refined in vitro and in vivo model systems are being used to validate the potential of identified therapeutic options, striving to provide sufficient pre-clinical evidence that allows the application of these newly found treatment opportunities in a clinical setting.
Stam RW, Schneider P, Hagelstein JAP, van der Linden MH, Stumpel DJPM, de Menezes RX, de Lorenzo P, Valsecchi MG, Pieters R. Gene expression profiling-based dissection of MLL-translocated and MLL-germline Acute Lymphoblastic Leukemia in infants. (2010) Blood 115(14):2835-2844. PubMed PMID: 20032505
Stumpel DJPM, Schneider P, van Roon EHJ, Boer JM, Lorenzo P, Valsecchi MG, de Menezes RX, Pieters R, Stam RW. Specific promoter methylation identifies different subgroups of MLL-rearranged infant Acute Lymphoblastic Leukemia, influences clinical outcome and provides therapeutic options. (2009) Blood 114(27):5490-5498. PubMed PMID: 19855078
Stumpel DJPM, Schneider P, Seslija L, Osaki H, Williams O, Pieters R, Stam RW. Connectivity mapping identifies HDAC inhibitors for the treatment of t(4;11)-positive infant acute lymphoblastic leukemia. (2012) Leukemia 26(4):682-692. PubMed PMID: 22015773
Spijkers-Hagelstein JA, Pinhanços SS, Schneider P, Pieters R, Stam RW. Chemical genomic screening identifies LY294002 as a modulator of glucocorticoid resistance in MLL-rearranged infant ALL. (2014) Leukemia 28(4):761-769. PubMed PMID: 23958920
Garrido Castro P, van Roon EHJ, Pinhanços SS, Trentin L, Schneider P, Kerstjens M, Te Kronnie G, Heidenreich O, Pieters R, Stam RW. The HDAC inhibitor panobinostat (LBH589) exerts in vivo anti-leukaemic activity against MLL-rearranged acute lymphoblastic leukaemia and involves the RNF20/RNF40/WAC-H2B ubiquitination axis. (2018) Leukemia 32(2):323-331. PubMed PMID: 28690313