Novel Approach Targets Leukemia’s Survival Route to Curb Recurrence

Building upon these findings, the team identified several drugs targeting pro-survival pre-B cell receptor signaling, that when combined with WEE1 inhibitors in a sequential treatment strategy, effectively counteracted drug tolerance, prevented recovery post-treatment and induced cell death in xenograft KMT2A-r models.

“Moving forward, we aim to investigate whether the changes in transcription factor activities are part of a broader stress response in leukemia¨. Specifically, we will explore whether chemotherapy agents used in standard leukemia protocols also contribute to the activation of a differentiated pre-B-like program, potentially leading to drug tolerance. We hope that this research will contribute to our understanding how drug treatments relate to cancer cell diversity and therapy resistance. The goal is to define effective combination therapies capable of countering heterogeneity and preventing disease recurrence.” says Olle Sangfelt,Principal Researcher at the Department of Cell and Molecular Biology.

Important collaboration partners

• The Institute of Biomedicine, School of Medicine, University of Eastern Finland,
• Division of Clinical Genetics, Department of Laboratory Medicine, Lund University,
• Tampere University Hospital

Main financiers of the study

The Swedish Childhood Cancer Fund, Swedish Cancer Society, The Swedish Research Council, the cancer Research Funds of Radiumhemmet, AstraZeneca, Academy of Finland, H2020 European Research Council,

Publication

Sequential drug treatment targeting cell cycle and cell fate regulatory programs blocks non-genetic cancer evolution in acute lymphoblastic leukemia.

Alena Malyukova¹*†, Mari Lahnalampi²†, Ton Falqués‑Costa³, Petri Pölönen², Mikko Sipola², Juha Mehtonen², Susanna Teppo⁴, Karen Akopyan¹, Johanna Viiliainen¹, Olli Lohi⁴, Anna K. Hagström‑Andersson³, Merja Heinäniemi²*† and Olle Sangfelt.

Genome Biology (2024) 25:143