Stam group

Some forms of acute leukemia have a poor prognosis and a high risk of recurrence after treatment. Our research group focuses on these forms. We investigate genetic characteristics to develop new treatment strategies.

The main focus of the Stam group has always been MLL-rearranged acute lymphoblastic leukemia (ALL) in infants (i.e. children <1 year of age), which represents a highly aggressive and difficult to treat type of childhood leukemia. Recently, however, we have expanded our focus by initiating research on high-risk types of pediatric acute myeloid leukemia (AML) characterized by MLL translocations or NUP98 gene fusions, in collaboration with Prof. dr. Michel Zwaan.

For these specific ALL and AML patient groups we aim to:

1. Understand the biology and (epi)genetics underlying

   a. leukemogenic transformation at pre-leukemic stages

   b. leukemia maintenance during full-blown overt leukemia

   c. disease relapse

2. Unravel the molecular mechanisms underlying drug resistance and therapy failure, and develop therapeutic opportunities to circumvent adverse drug responses

3. Identify and pre-clinically validate novel therapeutic targets and innovative treatment strategies, using refined in vitro and in vivo model systems.

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.