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Pauline Schneider

PhD Student
Pauline Schneider
Pauline Schneider
Epigenetic-based therapeutics for MLL-rearranged infant ALL: Mechanisms of acquired resistance and epigenetic plasticity
Phone +31 (0) 88 972 76 72

MLL-rearranged acute lymphoblastic leukemia (ALL) in infants (<1 year of age) is largely (if not solely) driven by inappropriate epigenetic events, and is most efficiently targeted by epigenetic-based drugs, including DNA demethylating agents, histone deacetylase (HDAC) inhibitors, inhibitors of BET bromodomain proteins, or inhibition of the histone methyltransferase DOT1L. However, leukemic cells have shown to readily acquire resistance to epigenetic-based drugs. Epigenetic plasticity allows leukemic cells to swiftly remodel their regulatory pathways, losing their dependency on the targeted epigenetic component and acquiring dependencies on alternative regulatory programs. My research aims to identify common regulatory pathways exploited by MLL-rearranged ALL cells to evade susceptibility to epigenetic-based drugs, and find therapeutic strategies that effectively block these escape routes, and thereby eliminating resistance to promising epigenetic-based therapies for MLL-rearranged infant ALL.

  • Hypoxic, glycolytic metabolism is a vulnerability of B-acute lymphoblastic leukemia-initiating cells

    • apr. 2022
    • Vivian, Morris, et al
    • Cell Reports
  • High-Throughput Drug Library Screening in Primary KMT2A-Rearranged Infant ALL Cells Favors the Identification of Drug Candidates That Activate P53 Signaling

    • mrt. 2022
    • Priscilla, Wander, et al
    • Biomedicines
  • Identification and characterization of relapse-initiating cells in MLL-rearranged infant ALL by single-cell transcriptomics

    • jan. 2022
    • Tito, Candelli, et al
    • Leukemia
  • Integrative methylome-transcriptome analysis unravels cancer cell vulnerabilities in infant MLLrearranged B cell acute lymphoblastic leukemia

    • jul. 2021
    • Juan Ramón, Tejedor, et al
    • Journal of Clinical Investigation
  • Irinotecan induces disease remission in xenograft mouse models of pediatric MLL-rearranged acute lymphoblastic leukemia

    • jul. 2021
    • Mark, Kerstjens, et al
    • Biomedicines
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