T-lineage acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that
requires treatment with intensified chemotherapy. Studies of the long-term effects of
chemotherapy in patients with T-ALL showed that recent gains in leukemia-free survival have been
achieved at the cost of significant increased rates of life-threatening and debilitating toxicities. Thus,
further advances in the treatment of T-ALL require the development of effective and highly specific
molecular targeted antileukemic drugs, thus requiring a better understanding of disease biology.
In the past, T-ALL biology research has largely been focused on the level of gene expression
analyses. However, recent advances in technology development have created unique opportunities
to assess translational regulation as an additional level of complexity implicated in the biology of
human T-ALL.
In this project, we hypothesise that aberrant activation of the translational machinery forms an
intrinsic part of the molecular circuitry that is perturbed in the pathogenesis of T-ALL. We strongly
believe that integrative analysis of ribosome profiling with state-of-the-art proteomics will provide
unique novel insights in the oncogenic reprogramming in human T-ALL at the translational level.
Therefore, we aim to identify the full spectrum of proteome diversity in malignant T cells and
investigate the proteogenomic consequences of targeting cap-dependent translation in molecular
genetic subtypes of T-ALL.