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Inge van Outersterp

PhD student
Inge van Outersterp

Achilles' heel of BCR-ABL1(-like) leukemia

Inge van Outersterp studied Molecular Life Sciences at the Radboud University in Nijmegen. After her graduation in 2019, she started working as a PhD student in the Den Boer group focusing on projects involving BCR-ABL1 positive and ABL-class B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Before the use of tyrosine kinase inhibitors (TKIs), such as imatinib, BCR-ABL1 positive BCP-ALL patients had a poor prognosis. The prognosis improved by inclusion of TKIs in the standard treatment protocol, but unfortunately about 30% of all BCR-ABL positive BCP-ALL patients still relapse or have refractory disease. These patients do not express resistance-associated mutations in their leukemic cells, suggesting a different nature of their poor response. The BCR-ABL1 project focuses on identifying new predictive biomarkers for TKI resistance, using RNA sequencing and Whole Exome Sequencing in combination with drug sensitivity assays. In parallel, we also study the efficacy of TKIs in ABL class patients who have a similar dismal outcome compared to BCR-ABL1 positive ALL in the pre-TKI era. We will develop fusion-specific Minimal Residual Disease (MRD) monitoring at the genomic DNA level to determine whether these molecular response parameters are a better predictor of therapy failure than Ig/TCR or flow-based MRD monitoring.